Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Müller-Tidow C, Steffen B, Cauvet T, Tickenbrock L, Ji P, Diederichs S, Sargin B, Köhler G, Stelljes M, Puccetti E, Ruthardt M, deVos S, Hiebert SW, Koeffler HP, Berdel WE, Serve H. Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells. Mol Cell Biol 2004;24:2890-904. [PMID: 15024077 PMCID: PMC371102 DOI: 10.1128/mcb.24.7.2890-2904.2004] [Citation(s) in RCA: 230] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open

For:	Müller-Tidow C, Steffen B, Cauvet T, Tickenbrock L, Ji P, Diederichs S, Sargin B, Köhler G, Stelljes M, Puccetti E, Ruthardt M, deVos S, Hiebert SW, Koeffler HP, Berdel WE, Serve H. Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells. Mol Cell Biol 2004;24:2890-904. [PMID: 15024077 PMCID: PMC371102 DOI: 10.1128/mcb.24.7.2890-2904.2004] [Citation(s) in RCA: 230] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open

Number

Cited by Other Article(s)

Wagstaff M, Sevim O, Goff A, Raynor M, Park H, Mancini EJ, Nguyen DTT, Chevassut T, Blair A, Castellano L, Newbury S, Towler B, Morgan RG. β-Catenin interacts with canonical RBPs including MSI2 to associate with a Wnt signalling mRNA network in myeloid leukaemia cells. Oncogene 2025:10.1038/s41388-025-03415-y. [PMID: 40301545 DOI: 10.1038/s41388-025-03415-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 04/02/2025] [Accepted: 04/09/2025] [Indexed: 05/01/2025]

Han Yu P, Yan Zhang Z, Yuan Kang Y, Huang P, Yang C, Naranmandura H. Acute myeloid leukemia with t(8;21) translocation: Molecular pathogenesis, potential therapeutics and future directions. Biochem Pharmacol 2025;233:116774. [PMID: 39864466 DOI: 10.1016/j.bcp.2025.116774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 12/18/2024] [Accepted: 01/21/2025] [Indexed: 01/28/2025]

Ide AD, Carpenter KA, Elaswad M, Opria K, Marcellin K, Gilliland C, Grainger S. Secreted Frizzled-Related Protein 1a regulates hematopoietic development in a dose-dependent manner. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.10.632371. [PMID: 39829913 PMCID: PMC11741364 DOI: 10.1101/2025.01.10.632371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/22/2025]

Yin Z, Yao Z, Chen D, Zhang Y, Weng G, Du X, Lin D, Xiao J, Sun Z, Zhang H, Liang X, Guo Z, Zhao W, Xuan L, Jiang X, Shi P, Liu Q, Ping B, Yu G. Homoharringtonine may help improve the outcomes of venetoclax and azacitidine in AML1-ETO positive acute myeloid leukemia. J Cancer Res Clin Oncol 2024;150:336. [PMID: 38969948 PMCID: PMC11226518 DOI: 10.1007/s00432-024-05861-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 06/19/2024] [Indexed: 07/07/2024]

Affiliation(s)

Zhao Yin Department of Hematology, Nanfang Hospital, Southern Medical University, No.1838, North of Guangzhou Avenue, Guangzhou City, Guangdong Province, 510515, P.R. China
Zurong Yao Department of Hematology, Nanfang Hospital, Southern Medical University, No.1838, North of Guangzhou Avenue, Guangzhou City, Guangdong Province, 510515, P.R. China
Dandan Chen Department of Hematology, Nanfang Hospital, Southern Medical University, No.1838, North of Guangzhou Avenue, Guangzhou City, Guangdong Province, 510515, P.R. China
Yu Zhang Department of Hematology, Nanfang Hospital, Southern Medical University, No.1838, North of Guangzhou Avenue, Guangzhou City, Guangdong Province, 510515, P.R. China
Guangyang Weng Department of Hematology, Shenzhen Second People's Hospital, Shenzhen, 518035, P.R. China
Xin Du Department of Hematology, Shenzhen Second People's Hospital, Shenzhen, 518035, P.R. China
Dongjun Lin Department of Hematology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, P.R. China
Jie Xiao Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, P.R. China
Zhiqiang Sun Department of Hematology, Shenzhen Hospital, Southern Medical University, Shenzhen, 510086, P.R. China
Hongyu Zhang Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, 518036, P.R. China
Xinquan Liang Department of Hematology, The First People Hospital of Chenzhou, Chenzhou, 423000, P.R. China
Ziwen Guo Department of Hematology, Zhongshan City People's Hospital, Zhongshan, 528403, P.R. China
Weihua Zhao Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530027, P.R. China
Li Xuan Department of Hematology, Nanfang Hospital, Southern Medical University, No.1838, North of Guangzhou Avenue, Guangzhou City, Guangdong Province, 510515, P.R. China
Xuejie Jiang Department of Hematology, Nanfang Hospital, Southern Medical University, No.1838, North of Guangzhou Avenue, Guangzhou City, Guangdong Province, 510515, P.R. China
Pengcheng Shi Department of Hematology, Nanfang Hospital, Southern Medical University, No.1838, North of Guangzhou Avenue, Guangzhou City, Guangdong Province, 510515, P.R. China
Qifa Liu Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, Guangzhou, 510515, P.R. China
Baohong Ping Department of Hematology, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, No.1838, North of Guangzhou Avenue, Guangzhou City, Guangdong Province, 510515, P.R. China.
Guopan Yu Department of Hematology, Nanfang Hospital, Southern Medical University, No.1838, North of Guangzhou Avenue, Guangzhou City, Guangdong Province, 510515, P.R. China.

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Wang C, Wang B, Mou Y, Liu X, Chen Q, Pu W, Rao Q, Wang C, Song J, Huang Y, Yan L, Huang L, Li Y. Design, Synthesis, and Anti-Leukemic Evaluation of a Series of Dianilinopyrimidines by Regulating the Ras/Raf/MEK/ERK and STAT3/c-Myc Pathways. Molecules 2024;29:1597. [PMID: 38611876 PMCID: PMC11013136 DOI: 10.3390/molecules29071597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 03/17/2024] [Accepted: 03/19/2024] [Indexed: 04/14/2024] Open

Abstract

Although the long-term survival rate for leukemia has made significant progress over the years with the development of chemotherapeutics, patients still suffer from relapse, leading to an unsatisfactory outcome. To discover the new effective anti-leukemia compounds, we synthesized a series of dianilinopyrimidines and evaluated the anti-leukemia activities of those compounds by using leukemia cell lines (HEL, Jurkat, and K562). The results showed that the dianilinopyrimidine analog H-120 predominantly displayed the highest cytotoxic potential in HEL cells. It remarkably induced apoptosis of HEL cells by activating the apoptosis-related proteins (cleaved caspase-3, cleaved caspase-9 and cleaved poly ADP-ribose polymerase (PARP)), increasing apoptosis protein Bad expression, and decreasing the expression of anti-apoptotic proteins (Bcl-2 and Bcl-xL). Furthermore, it induced cell cycle arrest in G2/M; concomitantly, we observed the activation of p53 and a reduction in phosphorylated cell division cycle 25C (p-CDC25C) / Cyclin B1 levels in treated cells. Additionally, the mechanism study revealed that H-120 decreased these phosphorylated signal transducers and activators of transcription 3, rat sarcoma, phosphorylated cellular RAF proto-oncogene serine / threonine kinase, phosphorylated mitogen-activated protein kinase kinase, phosphorylated extracellular signal-regulated kinase, and cellular myelocytomatosis oncogene (p-STAT3, Ras, p-C-Raf, p-MEK, p-MRK, and c-Myc) protein levels in HEL cells. Using the cytoplasmic and nuclear proteins isolation assay, we found for the first time that H-120 can inhibit the activation of STAT3 and c-Myc and block STAT3 phosphorylation and dimerization. Moreover, H-120 treatment effectively inhibited the disease progression of erythroleukemia mice by promoting erythroid differentiation into the maturation of erythrocytes and activating the immune cells. Significantly, H-120 also improved liver function in erythroleukemia mice. Therefore, H-120 may be a potential chemotherapeutic drug for leukemia patients.

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Affiliation(s)

Chaoyan Wang State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; (C.W.); (B.W.); (Y.M.); (X.L.); (Q.C.); (W.P.); (Q.R.); (C.W.); (J.S.); (Y.H.) Natural Products Research Center of Guizhou Province, Guiyang 550014, China College of Pharmacy, Guizhou Medical University, Guiyang 550004, China
Bo Wang State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; (C.W.); (B.W.); (Y.M.); (X.L.); (Q.C.); (W.P.); (Q.R.); (C.W.); (J.S.); (Y.H.) Natural Products Research Center of Guizhou Province, Guiyang 550014, China College of Basic Medical, Guizhou Medical University, Guiyang 550004, China
Yu Mou State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; (C.W.); (B.W.); (Y.M.); (X.L.); (Q.C.); (W.P.); (Q.R.); (C.W.); (J.S.); (Y.H.) Natural Products Research Center of Guizhou Province, Guiyang 550014, China College of Pharmacy, Guizhou Medical University, Guiyang 550004, China
Xiang Liu State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; (C.W.); (B.W.); (Y.M.); (X.L.); (Q.C.); (W.P.); (Q.R.); (C.W.); (J.S.); (Y.H.) Natural Products Research Center of Guizhou Province, Guiyang 550014, China College of Basic Medical, Guizhou Medical University, Guiyang 550004, China
Qiqing Chen State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; (C.W.); (B.W.); (Y.M.); (X.L.); (Q.C.); (W.P.); (Q.R.); (C.W.); (J.S.); (Y.H.) Natural Products Research Center of Guizhou Province, Guiyang 550014, China College of Pharmacy, Guizhou Medical University, Guiyang 550004, China
Weidong Pu State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; (C.W.); (B.W.); (Y.M.); (X.L.); (Q.C.); (W.P.); (Q.R.); (C.W.); (J.S.); (Y.H.) Natural Products Research Center of Guizhou Province, Guiyang 550014, China College of Pharmacy, Guizhou Medical University, Guiyang 550004, China
Qing Rao State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; (C.W.); (B.W.); (Y.M.); (X.L.); (Q.C.); (W.P.); (Q.R.); (C.W.); (J.S.); (Y.H.) Natural Products Research Center of Guizhou Province, Guiyang 550014, China
Chunlin Wang State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; (C.W.); (B.W.); (Y.M.); (X.L.); (Q.C.); (W.P.); (Q.R.); (C.W.); (J.S.); (Y.H.) Natural Products Research Center of Guizhou Province, Guiyang 550014, China
Jingrui Song State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; (C.W.); (B.W.); (Y.M.); (X.L.); (Q.C.); (W.P.); (Q.R.); (C.W.); (J.S.); (Y.H.) Natural Products Research Center of Guizhou Province, Guiyang 550014, China
Yubing Huang State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; (C.W.); (B.W.); (Y.M.); (X.L.); (Q.C.); (W.P.); (Q.R.); (C.W.); (J.S.); (Y.H.) Natural Products Research Center of Guizhou Province, Guiyang 550014, China
Longjia Yan School of Pharmaceutical Sciences, Guizhou University, Guiyang 550000, China
Lei Huang State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; (C.W.); (B.W.); (Y.M.); (X.L.); (Q.C.); (W.P.); (Q.R.); (C.W.); (J.S.); (Y.H.) Natural Products Research Center of Guizhou Province, Guiyang 550014, China
Yanmei Li State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; (C.W.); (B.W.); (Y.M.); (X.L.); (Q.C.); (W.P.); (Q.R.); (C.W.); (J.S.); (Y.H.) Natural Products Research Center of Guizhou Province, Guiyang 550014, China

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Monteith AJ, Ramsey HE, Silver AJ, Brown D, Greenwood D, Smith BN, Wise AD, Liu J, Olmstead SD, Watke J, Arrate MP, Gorska AE, Fuller L, Locasale JW, Stubbs MC, Rathmell JC, Savona MR. Lactate Utilization Enables Metabolic Escape to Confer Resistance to BET Inhibition in Acute Myeloid Leukemia. Cancer Res 2024;84:1101-1114. [PMID: 38285895 PMCID: PMC10984779 DOI: 10.1158/0008-5472.can-23-0291] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 08/08/2023] [Accepted: 01/24/2024] [Indexed: 01/31/2024]

Affiliation(s)

Andrew J. Monteith Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA Cancer Biology Program, Vanderbilt University School of Medicine, Nashville, TN, USA Department of Microbiology, University of Tennessee, Knoxville, TN, USA
Haley E. Ramsey Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA Cancer Biology Program, Vanderbilt University School of Medicine, Nashville, TN, USA
Alexander J. Silver Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA Cancer Biology Program, Vanderbilt University School of Medicine, Nashville, TN, USA
Donovan Brown Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
Dalton Greenwood Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA
Brianna N. Smith Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA Cancer Biology Program, Vanderbilt University School of Medicine, Nashville, TN, USA
Ashley D. Wise Department of Microbiology, University of Tennessee, Knoxville, TN, USA
Juan Liu Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA
Sarah D. Olmstead Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
Jackson Watke Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
Maria P. Arrate Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
Agnieszka E. Gorska Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
Londa Fuller Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
Jason W. Locasale Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA
Matthew C. Stubbs Incyte Corporation, Wilmington, DE, USA
Jeffrey C. Rathmell Cancer Biology Program, Vanderbilt University School of Medicine, Nashville, TN, USA Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA Vanderbilt Center for Immunobiology, Vanderbilt University School of Medicine, Nashville, TN, USA Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
Michael R. Savona Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA Cancer Biology Program, Vanderbilt University School of Medicine, Nashville, TN, USA Vanderbilt Center for Immunobiology, Vanderbilt University School of Medicine, Nashville, TN, USA Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA

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Marr AR, Halpin M, Corbin DL, Asemelash Y, Sher S, Gordon BK, Whipp EC, Mitchell S, Harrington BK, Orwick S, Benrashid S, Goettl VM, Yildiz V, Mitchell AD, Cahn O, Mims AS, Larkin KTM, Long M, Blachly J, Woyach JA, Lapalombella R, Grieselhuber NR. The multi-CDK inhibitor dinaciclib reverses bromo- and extra-terminal domain (BET) inhibitor resistance in acute myeloid leukemia via inhibition of Wnt/β-catenin signaling. Exp Hematol Oncol 2024;13:27. [PMID: 38438856 PMCID: PMC10913666 DOI: 10.1186/s40164-024-00483-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 01/23/2024] [Indexed: 03/06/2024] Open

Abstract

Acute myeloid leukemia (AML) is a highly aggressive hematologic cancer with poor survival across a broad range of molecular subtypes. Development of efficacious and well-tolerable therapies encompassing the range of mutations that can arise in AML remains an unmet need. The bromo- and extra-terminal domain (BET) family of proteins represents an attractive therapeutic target in AML due to their crucial roles in many cellular functions, regardless of any specific mutation. Many BET inhibitors (BETi) are currently in pre-clinical and early clinical development, but acquisition of resistance continues to remain an obstacle for the drug class. Novel methods to circumvent this development of resistance could be instrumental for the future use of BET inhibitors in AML, both as monotherapy and in combination. To date, many investigations into possible drug combinations of BETi with CDK inhibitors have focused on CDK9, which has a known physical and functional interaction with the BET protein BRD4. Therefore, we wished to investigate possible synergy and additive effects between inhibitors of these targets in AML. Here, we describe combination therapy with the multi-CDK inhibitor dinaciclib and the BETi PLX51107 in pre-clinical models of AML. Dinaciclib and PLX51107 demonstrate additive effects in AML cell lines, primary AML samples, and in vivo. Further, we demonstrate novel activity of dinaciclib through inhibition of the canonical/β-catenin dependent Wnt signaling pathway, a known resistance mechanism to BETi in AML. We show dinaciclib inhibits Wnt signaling at multiple levels, including downregulation of β-catenin, the Wnt co-receptor LRP6, as well as many Wnt pathway components and targets. Moreover, dinaciclib sensitivity remains unaffected in a setting of BET resistance, demonstrating similar inhibitory effects on Wnt signaling when compared to BET-sensitive cells. Ultimately, our results demonstrate rationale for combination CDKi and BETi in AML. In addition, our novel finding of Wnt signaling inhibition could have potential implications in other cancers where Wnt signaling is dysregulated and demonstrates one possible approach to circumvent development of BET resistance in AML.

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Affiliation(s)

Alexander R Marr Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Madeline Halpin Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Dominique L Corbin Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Yerdanos Asemelash Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Steven Sher Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Britten K Gordon Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Ethan C Whipp Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Shaneice Mitchell Department of Pathology, Stanford University, Stanford, CA, USA
Bonnie K Harrington College of Veterinary Medicine, Michigan State University, Lansing, MI, USA
Shelley Orwick Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Samon Benrashid Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Virginia M Goettl Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Vedat Yildiz Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA
Andrew D Mitchell Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Olivia Cahn Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Alice S Mims Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Karilyn T M Larkin Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Meixao Long Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
James Blachly Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA Leukemia Research Program, The Ohio State University James Comprehensive Cancer Center, Columbus, OH, USA
Jennifer A Woyach Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA Leukemia Research Program, The Ohio State University James Comprehensive Cancer Center, Columbus, OH, USA
Rosa Lapalombella Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA Leukemia Research Program, The Ohio State University James Comprehensive Cancer Center, Columbus, OH, USA
Nicole R Grieselhuber Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. Leukemia Research Program, The Ohio State University James Comprehensive Cancer Center, Columbus, OH, USA.

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Hu J, Huang R, Liang C, Wang Y, Wang M, Chen Y, Wu C, Zhang J, Liu Z, Zhao Q, Liu Z, Wang F, Yuan S. TRIM50 Inhibits Gastric Cancer Progression by Regulating the Ubiquitination and Nuclear Translocation of JUP. Mol Cancer Res 2023;21:1107-1119. [PMID: 37409971 PMCID: PMC10543995 DOI: 10.1158/1541-7786.mcr-23-0113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/04/2023] [Accepted: 06/28/2023] [Indexed: 07/07/2023]

Affiliation(s)

Jiajia Hu State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China
Runjie Huang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China
Chengcai Liang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China
Yingnan Wang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China
Min Wang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China
Yanxing Chen State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China
Chenyi Wu State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China
Jinling Zhang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China
Zekun Liu State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China
Qi Zhao State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China
Zexian Liu State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China
Feng Wang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China
Shuqiang Yuan State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China

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Yang T, Shi X, Li S, Zhao Z, Wang J, Yu P, Li H, Wang R, Chen Z. Targeting DHODH reveals therapeutic opportunities in ATRA-resistant acute promyelocytic leukemia. Biomed Pharmacother 2023;166:115314. [PMID: 37579695 DOI: 10.1016/j.biopha.2023.115314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 07/30/2023] [Accepted: 08/08/2023] [Indexed: 08/16/2023] Open

Affiliation(s)

Tingyuan Yang Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China
Xiayu Shi Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China
Shiliang Li Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China
Zhenjiang Zhao Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China
Junyi Wang Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China
Panpan Yu Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China
Honglin Li Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China; Innovation Center for AI and Drug Discovery, East China Normal University, Shanghai 200062, China; Lingang Laboratory, Shanghai 200031, China.
Rui Wang Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China.
Zhuo Chen Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China.

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Carpenter KA, Thurlow KE, Craig SEL, Grainger S. Wnt regulation of hematopoietic stem cell development and disease. Curr Top Dev Biol 2023;153:255-279. [PMID: 36967197 PMCID: PMC11104846 DOI: 10.1016/bs.ctdb.2022.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]

Shahid AM, Um IH, Elshani M, Zhang Y, Harrison DJ. NUC-7738 regulates β-catenin signalling resulting in reduced proliferation and self-renewal of AML cells. PLoS One 2022;17:e0278209. [PMID: 36520954 PMCID: PMC9754587 DOI: 10.1371/journal.pone.0278209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 11/13/2022] [Indexed: 12/23/2022] Open

Targeting β-catenin in acute myeloid leukaemia: past, present, and future perspectives. Biosci Rep 2022;42:231097. [PMID: 35352805 PMCID: PMC9069440 DOI: 10.1042/bsr20211841] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 03/14/2022] [Accepted: 03/30/2022] [Indexed: 11/24/2022] Open

Chen H, Wang J, Wang H, Liang J, Dong J, Bai H, Jiang G. Advances in the application of Let-7 microRNAs in the diagnosis, treatment and prognosis of leukemia. Oncol Lett 2021;23:1. [PMID: 34820000 PMCID: PMC8607238 DOI: 10.3892/ol.2021.13119] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 10/18/2021] [Indexed: 12/14/2022] Open

Torres-Montaner A. The telomere complex and the origin of the cancer stem cell. Biomark Res 2021;9:81. [PMID: 34736527 PMCID: PMC8567692 DOI: 10.1186/s40364-021-00339-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 10/21/2021] [Indexed: 11/15/2022] Open

Gajzer D, Logothetis CN, Sallman DA, Calon G, Babu A, Chan O, Vincelette ND, Volpe VO, Al Ali NH, Basra P, Talati C, Kuykendall AT, Mo Q, Padron E, Sweet K, Komrokji RS, Lancet JE, Yun S, Zhang L. MYC overexpression is associated with an early disease progression from MDS to AML. Leuk Res 2021;111:106733. [PMID: 34749168 DOI: 10.1016/j.leukres.2021.106733] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 10/09/2021] [Accepted: 10/19/2021] [Indexed: 10/20/2022]

Affiliation(s)

David Gajzer Department of Hematopathology and Laboratory Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Constantine N Logothetis University of South Florida, Internal Medicine, Tampa, FL, USA
David A Sallman Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
Gregoire Calon University of South Florida, College of Medicine, USA
Abida Babu University of South Florida, Internal Medicine, Tampa, FL, USA
Onyee Chan Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
Nicole D Vincelette Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
Virginia O Volpe Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
Najla H Al Ali Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
Pukhraz Basra Department of Hematopathology and Laboratory Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Chetasi Talati Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
Andrew T Kuykendall Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
Qianxing Mo Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Eric Padron Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
Kendra Sweet Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
Rami S Komrokji Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
Jeffrey E Lancet Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
Seongseok Yun Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Ling Zhang Department of Hematopathology and Laboratory Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

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Tang D, Luo Y, Jiang Y, Hu P, Peng H, Wu S, Zhang G, Wang Y. LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia. Cell Death Dis 2021;12:795. [PMID: 34404765 PMCID: PMC8371007 DOI: 10.1038/s41419-021-04080-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 07/06/2021] [Accepted: 07/06/2021] [Indexed: 12/23/2022]

Ahmadi SE, Rahimi S, Zarandi B, Chegeni R, Safa M. MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies. J Hematol Oncol 2021;14:121. [PMID: 34372899 PMCID: PMC8351444 DOI: 10.1186/s13045-021-01111-4] [Citation(s) in RCA: 102] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 06/12/2021] [Indexed: 12/17/2022] Open

Yun S, Vincelette ND, Yu X, Watson GW, Fernandez MR, Yang C, Hitosugi T, Cheng CH, Freischel AR, Zhang L, Li W, Hou H, Schaub FX, Vedder AR, Cen L, McGraw KL, Moon J, Murphy DJ, Ballabio A, Kaufmann SH, Berglund AE, Cleveland JL. TFEB links MYC signaling to epigenetic control of myeloid differentiation and acute myeloid leukemia. Blood Cancer Discov 2021;2:162-185. [PMID: 33860275 PMCID: PMC8043621 DOI: 10.1158/2643-3230.bcd-20-0029] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 10/30/2020] [Accepted: 12/15/2020] [Indexed: 12/20/2022] Open

Affiliation(s)

Seongseok Yun Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Nicole D Vincelette Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Xiaoqing Yu Department of Bioinformatics and Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Gregory W Watson Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Mario R Fernandez Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Chunying Yang Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Taro Hitosugi Department of Molecular Pharmacology and Experimental Therapeutics, and Department of Oncology, Mayo Clinic, Rochester, Minnesota
Chia-Ho Cheng Department of Bioinformatics and Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Audrey R Freischel Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Ling Zhang Department of Pathology and Laboratory Medicine, Tampa, Florida
Weimin Li Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Hsinan Hou Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
Franz X Schaub Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Alexis R Vedder Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Ling Cen Department of Bioinformatics and Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Kathy L McGraw Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Jungwon Moon Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Daniel J Murphy University of Glasgow, Institute of Cancer Sciences, Cancer Research UK Beatson Institute, Garscube Estate, Glasgow, United Kingdom
Andrea Ballabio Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy Medical Genetics Unit, Department of Medical and Translational Science, Federico II University, Naples, Italy Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas SSM School for Advanced Studies, Federico II University, Naples, Italy
Scott H Kaufmann Department of Molecular Pharmacology and Experimental Therapeutics, and Department of Oncology, Mayo Clinic, Rochester, Minnesota
Anders E Berglund Department of Bioinformatics and Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
John L Cleveland Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

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Caspi M, Wittenstein A, Kazelnik M, Shor-Nareznoy Y, Rosin-Arbesfeld R. Therapeutic targeting of the oncogenic Wnt signaling pathway for treating colorectal cancer and other colonic disorders. Adv Drug Deliv Rev 2021;169:118-136. [PMID: 33346022 DOI: 10.1016/j.addr.2020.12.010] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 12/10/2020] [Accepted: 12/14/2020] [Indexed: 02/08/2023]

Ramsey HE, Greenwood D, Zhang S, Childress M, Arrate MP, Gorska AE, Fuller L, Zhao Y, Stengel K, Fischer MA, Stubbs MC, Liu PCC, Boyd K, Rathmell JC, Hiebert SW, Savona MR. BET Inhibition Enhances the Antileukemic Activity of Low-dose Venetoclax in Acute Myeloid Leukemia. Clin Cancer Res 2021;27:598-607. [PMID: 33148670 DOI: 10.1158/1078-0432.ccr-20-1346] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 07/28/2020] [Accepted: 10/30/2020] [Indexed: 11/16/2022]

Affiliation(s)

Haley E Ramsey Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee Cancer Biology Program, Vanderbilt University School of Medicine, Nashville, Tennessee
Dalton Greenwood Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee
Susu Zhang Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee
Merrida Childress Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Maria P Arrate Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Agnieszka E Gorska Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Londa Fuller Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Yue Zhao Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee
Kristy Stengel Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee
Melissa A Fischer Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee Cancer Biology Program, Vanderbilt University School of Medicine, Nashville, Tennessee
Matthew C Stubbs Incyte Corporation, Wilmington, Delaware
Phillip C C Liu Incyte Corporation, Wilmington, Delaware
Kelli Boyd Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee
Jeffrey C Rathmell Cancer Biology Program, Vanderbilt University School of Medicine, Nashville, Tennessee Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee Vanderbilt Center for Immunobiology, Nashville, Tennessee Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
Scott W Hiebert Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
Michael R Savona Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee. Cancer Biology Program, Vanderbilt University School of Medicine, Nashville, Tennessee Vanderbilt Center for Immunobiology, Nashville, Tennessee Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee

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Dai Y, Cheng Z, Fricke DR, Zhao H, Huang W, Zhong Q, Zhu P, Zhang W, Wu Z, Lin Q, Zhu H, Liu Y, Qian T, Fu L, Cui L, Zeng T. Prognostic role of Wnt and Fzd gene families in acute myeloid leukaemia. J Cell Mol Med 2021;25:1456-1467. [PMID: 33417298 PMCID: PMC7875934 DOI: 10.1111/jcmm.16233] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 12/09/2020] [Accepted: 12/11/2020] [Indexed: 01/18/2023] Open

Affiliation(s)

Yifeng Dai Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.,Translational Medicine Center, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Zhiheng Cheng Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.,Translational Medicine Center, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Doerte R Fricke Department of Genetics, LSU Health Sciences Center, New Orleans, LA, USA
Hongyou Zhao Institute of Engineering Medicine, Beijing Institute of Technology, Beijing, China
Wenhui Huang Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Translational Medicine Center, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Qingfu Zhong Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Translational Medicine Center, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Pei Zhu Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Translational Medicine Center, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Wenjuan Zhang Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Translational Medicine Center, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Zhihua Wu Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Translational Medicine Center, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Qing Lin Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Translational Medicine Center, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Huoyan Zhu Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Translational Medicine Center, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Yan Liu Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, China
Tingting Qian Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Translational Medicine Center, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Lin Fu Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.,Department of Hematology, Huaihe Hospital of Henan University, Kaifeng, China.,Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumor Microenvironment, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
Longzhen Cui Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, China
Tiansheng Zeng Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Translational Medicine Center, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

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Frenquelli M, Tonon G. WNT Signaling in Hematological Malignancies. Front Oncol 2020;10:615190. [PMID: 33409156 PMCID: PMC7779757 DOI: 10.3389/fonc.2020.615190] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 11/16/2020] [Indexed: 12/19/2022] Open

Farweez BAT, Shalaby NA, Eissa DAG, Galal RESAM, El-khazragy N, Pessar SA. Lymphoid enhancer-binding factor 1 (LEF-1): a favorable prognostic factor in adult acute myeloid leukemia in Egyptian patients. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2020. [DOI: 10.1186/s43042-020-00073-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open

Abstract Abstract Background Canonical wingless-type (Wnt) signaling is a crucial pathway involved in normal hematopoiesis and the self-renewal process of hematopoietic stem cells. Deregulation of this pathway has been associated with different subtypes of leukemia. Lymphoid enhancer-binding factor 1 (LEF-1) is a major transcription factor of this pathway and plays a pivotal role in lymphoid differentiation and granulopoiesis. High LEF-1 expression has been reported as a prognostic marker in several types of adult hematological malignancies. We aimed to assess the prognostic utility of LEF-1 expression in adult de novo acute myeloid leukemia (AML) Egyptian patients in continuation of our previous work. LEF-1 expression was analyzed by real-time polymerase chain reaction (PCR) in 30 adults with newly diagnosed AML and remeasured at day 28 after induction therapy with the assessment of remission status. Results Patients were classified according to median expression level into high and low LEF-1 expression groups. LEF-1 levels were dramatically decreased following successful induction therapy. Also, high LEF-1 expression patients had a better response to therapy with better overall survival. ROC curve analysis of LEF-1 expression yielded a cutoff value of < 10.11 log10 (sensitivity of 90.48% and specificity of 100%) for predicting poor outcome. Univariate logistic regression analysis showed that for every log10 increase in the LEF-1 expression level, the chance of the patient to achieve hematological remission was increased by 2.29 folds. Conclusion Our study showed preliminary results that overexpression of LEF-1 is a favorable prognostic factor in newly diagnosed adult AML patients. The prognostic value of LEF-1 could suggest its utility for further risk classifications of AML and potentiality for being a target for therapy. Collapse

Zhao X, Shao P, Gai K, Li F, Shan Q, Xue HH. β-catenin and γ-catenin are dispensable for T lymphocytes and AML leukemic stem cells. eLife 2020;9:55360. [PMID: 32820720 PMCID: PMC7462606 DOI: 10.7554/elife.55360] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 08/14/2020] [Indexed: 02/07/2023] Open

Mastelaro de Rezende M, Zenker Justo G, Julian Paredes-Gamero E, Gosens R. Wnt-5A/B Signaling in Hematopoiesis throughout Life. Cells 2020;9:cells9081801. [PMID: 32751131 PMCID: PMC7465103 DOI: 10.3390/cells9081801] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 07/21/2020] [Accepted: 07/23/2020] [Indexed: 02/08/2023] Open

Ghandadi M, Valadan R, Mohammadi H, Akhtari J, Khodashenas S, Ashari S. Wnt-β-catenin Signaling Pathway, the Achilles' Heels of Cancer Multidrug Resistance. Curr Pharm Des 2020;25:4192-4207. [PMID: 31721699 DOI: 10.2174/1381612825666191112142943] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Accepted: 11/08/2019] [Indexed: 12/12/2022]

Soares-Lima SC, Pombo-de-Oliveira MS, Carneiro FRG. The multiple ways Wnt signaling contributes to acute leukemia pathogenesis. J Leukoc Biol 2020;108:1081-1099. [PMID: 32573851 DOI: 10.1002/jlb.2mr0420-707r] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 04/20/2020] [Accepted: 05/28/2020] [Indexed: 01/19/2023] Open

Xiao H, Liang S, Wang L. Competing endogenous RNA regulation in hematologic malignancies. Clin Chim Acta 2020;509:108-116. [PMID: 32479763 DOI: 10.1016/j.cca.2020.05.045] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 05/26/2020] [Accepted: 05/26/2020] [Indexed: 12/18/2022]

Qian J, Huang X, Zhang Y, Ye X, Qian W. γ-Catenin Overexpression in AML Patients May Promote Tumor Cell Survival via Activation of the Wnt/β-Catenin Axis. Onco Targets Ther 2020;13:1265-1276. [PMID: 32103994 PMCID: PMC7024797 DOI: 10.2147/ott.s230873] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Accepted: 02/03/2020] [Indexed: 12/14/2022] Open

Abstract

Background

Canonical Wnt/β-catenin signaling is frequently dysregulated in acute myeloid leukemia (AML) and has been implicated in leukemogenesis. γ-catenin was previously demonstrated to be associated with the nuclear localization of β-catenin, the central mediator, and to exert oncogenic effects in AML; however, the underlying mechanisms remain unclear. Our study aimed to investigate the expression characteristics of γ-catenin in AML patients, explore the mechanisms by which γ-catenin regulates β-catenin, and discuss the feasibility of targeting γ-catenin for AML treatment.

Methods

The mRNA expression levels of γ-catenin in AML patients were measured by qRT-PCR. Cell proliferation was examined via Cell Counting Kit-8 (CCK-8) assays. The expression levels of related proteins were measured via Western blotting. Specific siRNA was used to modulate the expression level of the γ-catenin gene. Apoptosis and cell cycle distribution were quantified by flow cytometry. The subcellular localization of γ-catenin and β-catenin was examined via immunofluorescence with a confocal laser scanning microscope.

Results

Overexpression of γ-catenin was frequently observed in AML and correlated with poor prognosis. Consistent with this finding, suppression of γ-catenin in the AML cell line THP-1 induced growth inhibition, promoted apoptosis and blocked β-catenin nuclear translocation. Interestingly, γ-catenin knockdown sensitized THP-1 cells to cytotoxic chemotherapeutic agents such as cytarabine and homoharringtonine and further inhibited β-catenin nuclear localization. Moreover, our data implied the relationship between γ-catenin and GSK3β (whose effect on β-catenin is mediated by its own phosphorylation), which may be the principal mechanism underlying the anti-AML effect of γ-catenin inhibition.

Conclusion

Taken together, our results revealed a potential role of γ-catenin in AML pathogenesis–mainly through the inhibition of GSK3β-mediated nuclear localization of β-catenin–and indicate that targeting γ-catenin might offer new AML treatments.

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Montoya JJ, Turnidge MA, Wai DH, Patel AR, Lee DW, Gokhale V, Hurley LH, Arceci RJ, Wetmore C, Azorsa DO. In vitro activity of a G-quadruplex-stabilizing small molecule that synergizes with Navitoclax to induce cytotoxicity in acute myeloid leukemia cells. BMC Cancer 2019;19:1251. [PMID: 31881855 PMCID: PMC6935221 DOI: 10.1186/s12885-019-6464-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 12/15/2019] [Indexed: 12/28/2022] Open

Abstract

Background

Acute Myeloid Leukemia (AML) is a malignancy of myeloid precursor cells that arise from genomic alterations in the expression of key growth regulatory genes causing cells to assume an undifferentiated state and continue to proliferate. Recent efforts have focused on developing therapies that target specific protein products of aberrantly expressed genes. However, many of the identified proteins are difficult to target and thought to be “undrugable” because of structural challenges, protein overexpression, or mutations that confer resistance to therapy. A novel technology that circumvents some of these issues is the use of small molecules that stabilize secondary DNA structures present in the promoters of many potential oncogenes and modulate their transcription.

Methods

This study characterizes the in vitro activity of the G-quadruplex-stabilizing small molecule GQC-05 in AML cells. The effect of GQC-05 on three AML cell lines was analyzed using viability and apoptosis assays. GQC-05 has been shown to down-regulate MYC through G-quadruplex stabilization in Burkitt’s lymphoma cell lines. MYC expression was evaluated through qPCR and immunoblotting in the three AML cell lines following the treatment of GQC-05. In order to identify other therapeutic agents that potentiate the activity of GQC-05, combination drug screening was performed. The drug combinations were validated using in vitro cytotoxicity assays and compared to other commonly used chemotherapeutic agents.

Results

GQC-05 treatment of KG-1a, CMK and TF-1 cells decreased cell viability and resulted in increased DNA damage and apoptosis. Additionally, treatment of KG-1a, CMK and TF-1 with GQC-05 resulted in decreased expression of MYC mRNA and protein, with a more pronounced effect in KG-1a cells. Combination drug screening identified the Bcl-2/Bcl-X_L inhibitor Navitoclax as a compound that potentiated GQC-05 activity. Co-treatment with GQC-05 and Navitoclax showed a synergistic decrease in cell viability of AML cells as determined by Chou-Talalay analysis, and induced more DNA damage, apoptosis, and rapid cytotoxicity. The cytotoxicity induced by GQC-05 and Navitoclax was more potent than that of Navitoclax combined with either cytarabine or doxorubicin.

Conclusion

These results suggest that the G-quadruplex stabilizing small molecule GQC-05 induces down regulated MYC expression and DNA damage in AML cells. Treatment with both GQC-05 with a Bcl-2/Bcl-X_L inhibitor Navitoclax results in increased cytotoxic activity, which is more pronounced than Navitoclax or GQC-05 alone, and more significant than Navitoclax in combination with cytarabine and doxorubicin that are currently being used clinically.

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Affiliation(s)

Justin J Montoya The Institute of Molecular Medicine at Phoenix Children's Hospital, 475 N 5th Street, Phoenix, AZ, 85004, USA. .,Department of Child Health, The University of Arizona College of Medicine-Phoenix, 475 N 5th Street, Phoenix, AZ, 85004, USA.
Megan A Turnidge The Institute of Molecular Medicine at Phoenix Children's Hospital, 475 N 5th Street, Phoenix, AZ, 85004, USA.,Department of Child Health, The University of Arizona College of Medicine-Phoenix, 475 N 5th Street, Phoenix, AZ, 85004, USA.,School of Life Sciences, Arizona State University, Tempe, AZ, USA.,Present Address: Department of Molecular & Medical Genetics, Oregon Health and Science University, Portland, OR, 97239, USA
Daniel H Wai The Institute of Molecular Medicine at Phoenix Children's Hospital, 475 N 5th Street, Phoenix, AZ, 85004, USA.,Department of Child Health, The University of Arizona College of Medicine-Phoenix, 475 N 5th Street, Phoenix, AZ, 85004, USA
Apurvi R Patel The Institute of Molecular Medicine at Phoenix Children's Hospital, 475 N 5th Street, Phoenix, AZ, 85004, USA.,Department of Child Health, The University of Arizona College of Medicine-Phoenix, 475 N 5th Street, Phoenix, AZ, 85004, USA.,Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, USA
David W Lee The Institute of Molecular Medicine at Phoenix Children's Hospital, 475 N 5th Street, Phoenix, AZ, 85004, USA.,Department of Child Health, The University of Arizona College of Medicine-Phoenix, 475 N 5th Street, Phoenix, AZ, 85004, USA
Vijay Gokhale University of Arizona College of Pharmacy, Tucson, AZ, USA
Laurence H Hurley University of Arizona College of Pharmacy, Tucson, AZ, USA
Robert J Arceci The Institute of Molecular Medicine at Phoenix Children's Hospital, 475 N 5th Street, Phoenix, AZ, 85004, USA.,Department of Child Health, The University of Arizona College of Medicine-Phoenix, 475 N 5th Street, Phoenix, AZ, 85004, USA.,Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, USA
Cynthia Wetmore The Institute of Molecular Medicine at Phoenix Children's Hospital, 475 N 5th Street, Phoenix, AZ, 85004, USA.,Department of Child Health, The University of Arizona College of Medicine-Phoenix, 475 N 5th Street, Phoenix, AZ, 85004, USA.,Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, USA
David O Azorsa The Institute of Molecular Medicine at Phoenix Children's Hospital, 475 N 5th Street, Phoenix, AZ, 85004, USA.,Department of Child Health, The University of Arizona College of Medicine-Phoenix, 475 N 5th Street, Phoenix, AZ, 85004, USA.,Present Address: Systems Oncology, Scottsdale, AZ, 85255, USA

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Bigas A, Guillén Y, Schoch L, Arambilet D. Revisiting β-Catenin Signaling in T-Cell Development and T-Cell Acute Lymphoblastic Leukemia. Bioessays 2019;42:e1900099. [PMID: 31854474 DOI: 10.1002/bies.201900099] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 11/28/2019] [Indexed: 12/25/2022]

Beghini A. Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription. Cancers (Basel) 2019;11:E1973. [PMID: 31817911 PMCID: PMC6966602 DOI: 10.3390/cancers11121973] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 12/02/2019] [Accepted: 12/05/2019] [Indexed: 11/25/2022] Open

Clara JA, Monge C, Yang Y, Takebe N. Targeting signalling pathways and the immune microenvironment of cancer stem cells - a clinical update. Nat Rev Clin Oncol 2019;17:204-232. [PMID: 31792354 DOI: 10.1038/s41571-019-0293-2] [Citation(s) in RCA: 487] [Impact Index Per Article: 81.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/14/2019] [Indexed: 02/06/2023]

Mudgapalli N, Nallasamy P, Chava H, Chava S, Pathania AS, Gunda V, Gorantla S, Pandey MK, Gupta SC, Challagundla KB. The role of exosomes and MYC in therapy resistance of acute myeloid leukemia: Challenges and opportunities. Mol Aspects Med 2019;70:21-32. [PMID: 31623866 PMCID: PMC7775410 DOI: 10.1016/j.mam.2019.10.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 09/27/2019] [Accepted: 10/06/2019] [Indexed: 12/12/2022]

Abstract

Acute myeloid leukemia (AML) is caused by abnormal production of white blood cells, red blood cells or platelets. The leukemia cells communicate with their microenvironment through nano-vesicle exosomes that are 30-100 nm in diameter. These nano-vesicles are released from body fluids upon fusion of an endocytic compartment with the cell membrane. Exosomes function as cargo to deliver signaling molecules to distant cells. This allows cross-talk between hematopoietic cells and other distant target cell environments. Exosomes support leukemia growth by acting as messengers between tumor cells and the microenvironment as well as inducing oncogenic factors such as c-Myc. Exosomes have also been used as biomarkers in the clinical diagnosis of leukemia. Glycogen synthase kinase-3 (GSK-3) and protein phosphatase 2A (PP2A) are two crucial signaling molecules involved in the AML pathogenesis and MYC stability. GSK-3 is a serine/threonine protein kinase that coordinates with over 40 different proteins during physiological/pathological conditions in blood cells. The dysregulation in GSK-3 has been reported during hematological malignancies. GSK-3 acts as a tumor suppressor by targeting c-MYC, MCL-1 and β-catenin. Conversely, GSK-3 can also act as tumor promoter in some instances. The pharmacological modulators of GSK-3 such as ABT-869, 6-Bromoindirubin-3'-oxime (BIO), GS-87 and LY2090314 have shown promise in the treatment of hematological malignancy. PP2A is a heterotrimeric serine/threonine phosphatase involved in the regulation of hematological malignancy. PP2A-activating drugs (PADs) can effectively antagonize leukemogenesis. The discovery of exosomes, kinase inhibitors and phosphatase activators have provided new hope to the leukemia patients. This review discusses the role of exosomes, GSK-3 and PP2A in the pathogenesis of leukemia. We provide evidence from both preclinical and clinical studies.

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Wnt Signalling in Acute Myeloid Leukaemia. Cells 2019;8:cells8111403. [PMID: 31703382 PMCID: PMC6912424 DOI: 10.3390/cells8111403] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 10/31/2019] [Accepted: 11/06/2019] [Indexed: 12/13/2022] Open

Wnt Signaling in the Regulation of Immune Cell and Cancer Therapeutics. Cells 2019;8:cells8111380. [PMID: 31684152 PMCID: PMC6912555 DOI: 10.3390/cells8111380] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2019] [Revised: 10/21/2019] [Accepted: 11/01/2019] [Indexed: 12/17/2022] Open

El-Khazragy N, Elayat W, Matbouly S, Seliman S, Sami A, Safwat G, Diab A. The prognostic significance of the long non-coding RNAs "CCAT1, PVT1" in t(8;21) associated Acute Myeloid Leukemia. Gene 2019;707:172-177. [PMID: 30943439 DOI: 10.1016/j.gene.2019.03.055] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Revised: 03/13/2019] [Accepted: 03/25/2019] [Indexed: 12/13/2022]

Häfner AK, Kahnt AS, Steinhilber D. Beyond leukotriene formation—The noncanonical functions of 5-lipoxygenase. Prostaglandins Other Lipid Mediat 2019;142:24-32. [DOI: 10.1016/j.prostaglandins.2019.03.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 03/14/2019] [Accepted: 03/25/2019] [Indexed: 01/17/2023]

Giri B, Gupta VK, Yaffe B, Modi S, Roy P, Sethi V, Lavania SP, Vickers SM, Dudeja V, Banerjee S, Watts J, Saluja A. Pre-clinical evaluation of Minnelide as a therapy for acute myeloid leukemia. J Transl Med 2019;17:163. [PMID: 31109340 PMCID: PMC6528210 DOI: 10.1186/s12967-019-1901-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 04/30/2019] [Indexed: 01/22/2023] Open

Abstract

Background

There is an urgent need for novel and effective treatment options for acute myeloid leukemia (AML). Triptolide, a diterpenoid tri-epoxide compound isolated from the herb Tripterygium wilfordii and its water-soluble pro-drug-Minnelide have shown promising anti-cancer activity. A recent clinical trial for patients with solid tumors confirmed the safety and efficacy at biologically equivalent doses of 0.2 mg/kg/day and lower.

Methods

Cell viability of multiple AML cell lines as well as patient apheresis samples were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) based assay. Apoptosis was evaluated by estimating the amount of cleaved caspase. AML cell line (THP1-Luc) was implanted in immunocompromised mice and treated with indicated doses of Minnelide. Leukemic burden before and after treatment was evaluated by imaging in an In Vivo Imaging System (IVIS).

Results

In the current study, we show that Minnelide, at doses below maximum tolerated dose (MTD) demonstrates leukemic clearance of both primary AML blasts and luciferase expressing THP-1 cells in mice. In vitro, multiple primary AML apheresis samples and AML cell lines (THP-1, KG1, Kasumi-1, HL-60) were sensitive to triptolide mediated cell death and apoptosis in low doses. Treatment with triptolide led to a significant decrease in the colony forming ability of AML cell lines as well as in the expression of stem cell markers. Additionally, it resulted in the cell cycle arrest in the G1/S phase with significant downregulation of c-Myc, a major transcriptional regulator mediating cancer cell growth and stemness.

Conclusion

Our results suggest that Minnelide, with confirmed safety and activity in the clinic, exerts a potent anti-leukemic effect in multiple models of AML at doses easily achievable in patients.

Electronic supplementary material

The online version of this article (10.1186/s12967-019-1901-8) contains supplementary material, which is available to authorized users.

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Affiliation(s)

Bhuwan Giri Sylvester Comprehensive Cancer Center and DeWitt Daughtry Family Department of Surgery, University of Miami, 460C CRB Research Building, 1140 NW 14th St, Miami, FL, 33136, USA
Vineet K Gupta Sylvester Comprehensive Cancer Center and DeWitt Daughtry Family Department of Surgery, University of Miami, 460C CRB Research Building, 1140 NW 14th St, Miami, FL, 33136, USA
Brianna Yaffe Sylvester Comprehensive Cancer Center and DeWitt Daughtry Family Department of Surgery, University of Miami, 460C CRB Research Building, 1140 NW 14th St, Miami, FL, 33136, USA
Shrey Modi Sylvester Comprehensive Cancer Center and DeWitt Daughtry Family Department of Surgery, University of Miami, 460C CRB Research Building, 1140 NW 14th St, Miami, FL, 33136, USA
Pooja Roy Sylvester Comprehensive Cancer Center and DeWitt Daughtry Family Department of Surgery, University of Miami, 460C CRB Research Building, 1140 NW 14th St, Miami, FL, 33136, USA
Vrishketan Sethi Sylvester Comprehensive Cancer Center and DeWitt Daughtry Family Department of Surgery, University of Miami, 460C CRB Research Building, 1140 NW 14th St, Miami, FL, 33136, USA
Shweta P Lavania Sylvester Comprehensive Cancer Center and DeWitt Daughtry Family Department of Surgery, University of Miami, 460C CRB Research Building, 1140 NW 14th St, Miami, FL, 33136, USA
Selwyn M Vickers Sylvester Comprehensive Cancer Center and DeWitt Daughtry Family Department of Surgery, University of Miami, 460C CRB Research Building, 1140 NW 14th St, Miami, FL, 33136, USA
Vikas Dudeja Sylvester Comprehensive Cancer Center and DeWitt Daughtry Family Department of Surgery, University of Miami, 460C CRB Research Building, 1140 NW 14th St, Miami, FL, 33136, USA
Sulagna Banerjee Sylvester Comprehensive Cancer Center and DeWitt Daughtry Family Department of Surgery, University of Miami, 460C CRB Research Building, 1140 NW 14th St, Miami, FL, 33136, USA
Justin Watts Sylvester Comprehensive Cancer Center and DeWitt Daughtry Family Department of Surgery, University of Miami, 460C CRB Research Building, 1140 NW 14th St, Miami, FL, 33136, USA
Ashok Saluja Sylvester Comprehensive Cancer Center and DeWitt Daughtry Family Department of Surgery, University of Miami, 460C CRB Research Building, 1140 NW 14th St, Miami, FL, 33136, USA.

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Luong-Gardiol N, Siddiqui I, Pizzitola I, Jeevan-Raj B, Charmoy M, Huang Y, Irmisch A, Curtet S, Angelov GS, Danilo M, Juilland M, Bornhauser B, Thome M, Hantschel O, Chalandon Y, Cazzaniga G, Bourquin JP, Huelsken J, Held W. γ-Catenin-Dependent Signals Maintain BCR-ABL1⁺ B Cell Acute Lymphoblastic Leukemia. Cancer Cell 2019;35:649-663.e10. [PMID: 30991025 DOI: 10.1016/j.ccell.2019.03.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Revised: 01/29/2019] [Accepted: 03/14/2019] [Indexed: 11/23/2022]

Affiliation(s)

Noemie Luong-Gardiol Department of Oncology UNIL CHUV, University of Lausanne, Epalinges, Switzerland
Imran Siddiqui Department of Oncology UNIL CHUV, University of Lausanne, Epalinges, Switzerland
Irene Pizzitola Department of Oncology UNIL CHUV, University of Lausanne, Epalinges, Switzerland
Beena Jeevan-Raj Department of Oncology UNIL CHUV, University of Lausanne, Epalinges, Switzerland
Mélanie Charmoy Department of Oncology UNIL CHUV, University of Lausanne, Epalinges, Switzerland
Yun Huang Department of Pediatric Oncology and Children's Research Centre, University Children's Hospital Zürich, Zürich, Switzerland
Anja Irmisch Swiss Institute for Experimental Cancer Research (ISREC), Federal University of Technology Lausanne (EPFL), Lausanne, Switzerland
Sara Curtet Department of Oncology UNIL CHUV, University of Lausanne, Epalinges, Switzerland
Georgi S Angelov Department of Oncology UNIL CHUV, University of Lausanne, Epalinges, Switzerland
Maxime Danilo Department of Oncology UNIL CHUV, University of Lausanne, Epalinges, Switzerland
Mélanie Juilland Department of Biochemistry, University of Lausanne, Epalinges, Switzerland
Beat Bornhauser Department of Pediatric Oncology and Children's Research Centre, University Children's Hospital Zürich, Zürich, Switzerland
Margot Thome Department of Biochemistry, University of Lausanne, Epalinges, Switzerland
Oliver Hantschel Swiss Institute for Experimental Cancer Research (ISREC), Federal University of Technology Lausanne (EPFL), Lausanne, Switzerland
Yves Chalandon Service d'Hématologie, Hôpitaux Universitaire de Genève, Geneva, Switzerland
Gianni Cazzaniga Centro Ricerca Tettamanti, Pediatric Clinic University of Milano-Bicocca, Monza, Italy
Jean-Pierre Bourquin Department of Pediatric Oncology and Children's Research Centre, University Children's Hospital Zürich, Zürich, Switzerland
Joerg Huelsken Swiss Institute for Experimental Cancer Research (ISREC), Federal University of Technology Lausanne (EPFL), Lausanne, Switzerland
Werner Held Department of Oncology UNIL CHUV, University of Lausanne, Epalinges, Switzerland.

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Chatterjee S, Sil PC. Targeting the crosstalks of Wnt pathway with Hedgehog and Notch for cancer therapy. Pharmacol Res 2019;142:251-261. [PMID: 30826456 DOI: 10.1016/j.phrs.2019.02.027] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 01/23/2019] [Accepted: 02/25/2019] [Indexed: 12/12/2022]

Fetisov TI, Lesovaya EA, Yakubovskaya MG, Kirsanov KI, Belitsky GA. Alterations in WNT Signaling in Leukemias. BIOCHEMISTRY (MOSCOW) 2019;83:1448-1458. [PMID: 30878020 DOI: 10.1134/s0006297918120039] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]

Liu G, Liu S, Cao G, Luo W, Li P, Wang S, Chen Y. SPAG5 contributes to the progression of gastric cancer by upregulation of Survivin depend on activating the wnt/β-catenin pathway. Exp Cell Res 2019;379:83-91. [PMID: 30904482 DOI: 10.1016/j.yexcr.2019.03.024] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 03/14/2019] [Accepted: 03/16/2019] [Indexed: 02/07/2023]

Tang G, Hu S, Wang SA, Xie W, Lin P, Xu J, Toruner G, Zhao M, Gu J, Doty M, Li S, Medeiros LJ, Tang Z. t(3;8)(q26.2;q24) Often Leads to MECOM/MYC Rearrangement and Is Commonly Associated with Therapy-Related Myeloid Neoplasms and/or Disease Progression. J Mol Diagn 2019;21:343-351. [DOI: 10.1016/j.jmoldx.2018.10.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 10/09/2018] [Accepted: 10/26/2018] [Indexed: 01/06/2023] Open

Chong PSY, Zhou J, Chooi JY, Chan ZL, Toh SHM, Tan TZ, Wee S, Gunaratne J, Zeng Q, Chng WJ. Non-canonical activation of β-catenin by PRL-3 phosphatase in acute myeloid leukemia. Oncogene 2019;38:1508-1519. [PMID: 30305722 DOI: 10.1038/s41388-018-0526-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 09/13/2018] [Accepted: 09/17/2018] [Indexed: 11/09/2022]

Morgan RG, Ridsdale J, Payne M, Heesom KJ, Wilson MC, Davidson A, Greenhough A, Davies S, Williams AC, Blair A, Waterman ML, Tonks A, Darley RL. LEF-1 drives aberrant β-catenin nuclear localization in myeloid leukemia cells. Haematologica 2019;104:1365-1377. [PMID: 30630973 PMCID: PMC6601079 DOI: 10.3324/haematol.2018.202846] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 01/03/2019] [Indexed: 12/24/2022] Open

Ohanian M, Rozovski U, Kanagal-Shamanna R, Abruzzo LV, Loghavi S, Kadia T, Futreal A, Bhalla K, Zuo Z, Huh YO, Post SM, Ruvolo P, Garcia-Manero G, Andreeff M, Kornblau S, Borthakur G, Hu P, Medeiros LJ, Takahashi K, Hornbaker MJ, Zhang J, Nogueras-González GM, Huang X, Verstovsek S, Estrov Z, Pierce S, Ravandi F, Kantarjian HM, Bueso-Ramos CE, Cortes JE. MYC protein expression is an important prognostic factor in acute myeloid leukemia. Leuk Lymphoma 2019;60:37-48. [PMID: 29741984 PMCID: PMC6226369 DOI: 10.1080/10428194.2018.1464158] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]

Affiliation(s)

Maro Ohanian Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Uri Rozovski Department of Hematology, Davidoff Cancer Center at Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Israel
Rashmi Kanagal-Shamanna Department of Hematopathology, The University of Texas at MD Anderson Cancer Center Houston, Texas
Lynne V. Abruzzo Department of Pathology, Ohio State University, Columbus, OH 43202
Sanam Loghavi Department of Hematopathology, The University of Texas at MD Anderson Cancer Center Houston, Texas
Tapan Kadia Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Andrew Futreal Department of Genomic Medicine, The University of Texas at MD Anderson Cancer Center, Houston, TX
Kapil Bhalla Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Zhuang Zuo Department of Hematopathology, The University of Texas at MD Anderson Cancer Center Houston, Texas
Yang O. Huh Department of Hematopathology, The University of Texas at MD Anderson Cancer Center Houston, Texas
Sean M. Post Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Peter Ruvolo Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Guillermo Garcia-Manero Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Michael Andreeff Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Steven Kornblau Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Gautam Borthakur Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Peter Hu School of Health Professions, The University of Texas at MD Anderson Cancer Center, Houston, TX
L. Jeffrey Medeiros Department of Hematopathology, The University of Texas at MD Anderson Cancer Center Houston, Texas
Koichi Takahashi Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Marisa J. Hornbaker Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Jianhua Zhang Department of Genomic Medicine, The University of Texas at MD Anderson Cancer Center, Houston, TX
Graciela M. Nogueras-González Department of Biostatistics, The University of Texas at MD Anderson Cancer Center, Houston, TX
Xuelin Huang Department of Biostatistics, The University of Texas at MD Anderson Cancer Center, Houston, TX
Srdan Verstovsek Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Zeev Estrov Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Sherry Pierce Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Farhad Ravandi Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Hagop M. Kantarjian Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas
Carlos E. Bueso-Ramos Department of Hematopathology, The University of Texas at MD Anderson Cancer Center Houston, Texas
Jorge E. Cortes Department of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, Texas

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Evaluation of the Gene Expression of the Cytoprotective Proteins in Response to Daunorubicin in U937 Cells. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2018. [DOI: 10.5812/ijcm.10044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]

Chen C, Huang X, Wang K, Chen K, Gao D, Qian S. Early mortality in acute promyelocytic leukemia: Potential predictors. Oncol Lett 2018;15:4061-4069. [PMID: 29541170 PMCID: PMC5835847 DOI: 10.3892/ol.2018.7854] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 12/08/2017] [Indexed: 01/18/2023] Open

Aktary Z, Alaee M, Pasdar M. Beyond cell-cell adhesion: Plakoglobin and the regulation of tumorigenesis and metastasis. Oncotarget 2018;8:32270-32291. [PMID: 28416759 PMCID: PMC5458283 DOI: 10.18632/oncotarget.15650] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Accepted: 12/16/2016] [Indexed: 12/13/2022] Open