• acute myeloid leukemia
• chronic lymphocytic leukemia
• complete remission
• rituximab
• venetoclax

• B1
• CD11b
• CLL/lymphoma
• Hamp2
• TC+ Tg
• V2-5

The Coexistence of myeloid and lymphoid malignancies is rare. Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies. Synchronous diagnoses of diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML), and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) in the same patient have not been reported. Here we report one such case.

An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL. The bone marrow and peripheral blood contained two groups of cells. One group of cells fulfilled the criteria of AML, and the other revealed the features of small B lymphocytic proliferative disorder, which we considered LPL/WM. Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells, including ATM deletion, CCND1 amplification, mutations of MYD88 (L265P) and TP53, WT1 overexpression, and fusion gene of BIRC2-ARAP1, as well as complex chromosomal abnormalities. The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis.

The coexistence of DLBCL, AML, and untreated LPL/WM in the same patient is extremely rare, which probably results from multiple steps of genetic abnormalities. Asymptomatic LPL/WM might have occurred first, then myelodysplastic syndrome-related AML developed, and finally aggressive DLBCL arose. Therefore, medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.

• Diffuse large B-cell lymphoma
• Acute myeloid leukemia
• Small B lymphocyte proliferative disorder
• Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia
• Coexistence
• Case report

Concomitant diagnosis of non-Hodgkin lymphoma (NHL) and acute myeloid leukemia secondary to chronic myeloproliferative neoplasms (MPNs) is rarely reported. Patients with MPNs may have a second neoplasm, and the risk of lymphoid line neoplasms is 2.5-3.5 times for lymphoid line neoplasms. The explanation for this association is the genetic instability of hematopoietic progenitors in MPNs. An 80-year-old Caucasian man, with many comorbidities, presents for physical asthenia, sweating. The right inguinal adenopathy was known one month before the examination. The patient was diagnosed concomitantly with diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) secondary to primary myelofibrosis (PMF) and presented trisomy 8, trisomy 13, and triple-negative PMF status. The patient initially received two well-tolerated R mini CHOP series. This type of treatment was selected to treat DLBCL for one unfit patient for intensive chemotherapy due to his age and comorbidities. R mini CHOP administration was followed by severe aplasia that lasted approximately two weeks followed by severe thrombocytosis that reached 4000 x109/L, and Thromboreductin recommendation was mandatory. The result of the treatment was a partial response but with severe adverse events like neutropenia G4, due to the delay of the treatment the patient lost the response. It was mandatory to select another treatment line and the chosen was venetoclax; it was selected for the simultaneous treatment of DLBCL and the underlying AML. It was obtained a significant reduction in the size of the inguinal lymph node block in two weeks of treatment. Severe neutropenia was diagnosed and complicated with sepsis. The evolution is unfavorable with the installation of multiple organ dysfunction. The presence of a complex karyotype (trisomy 8, trisomy 13) in a patient with myeloid metaplasia with triple-negative PMF was associated with blast transformation and severe thrombocytosis. The patient was diagnosed concomitantly with DLBCL, making the therapeutic decision difficult. Venetoclax has been shown to be useful in the treatment of DLBCL but has been associated with severe neutropenia, which has led to infectious complications.

• leukemia
• myelodysplastic syndromes
• myeloid
• myeloproliferative disorders

Acute myeloid leukemia (AML) is an extremely heterogeneous malignant disorder; AML has been reported as one of the main causes of death in children. The objective of this work was to classify the most deleterious mutation in CCAAT/enhancer-binding protein-alpha (CEBPA) and to predict their influence on the functional, structural, and expression levels by various Bioinformatics analysis tools.

The single nucleotide polymorphisms (SNPs) were claimed from the National Center for Biotechnology Information (NCBI) database and then submitted into various functional analysis tools, which were done to predict the influence of each SNP, followed by structural analysis of modeled protein followed by predicting the mutation effect on energy stability; the most damaging mutations were chosen for additional investigation by Mutation3D, Project hope, ConSurf, BioEdit, and UCSF Chimera tools.

A total of 5 mutations out of 248 were likely to be responsible for the structural and functional variations in CEBPA protein, whereas in the 3′-untranslated region (3′-UTR) the result showed that among 350 SNPs in the 3′-UTR of CEBPA gene, about 11 SNPs were predicted. Among these 11 SNPs, 65 alleles disrupted a conserved miRNA site and 22 derived alleles created a new site of miRNA.

In this study, the impact of functional mutations in the CEBPA gene was investigated through different bioinformatics analysis techniques, which determined that R339W, R288P, N292S, N292T, and D63N are pathogenic mutations that have a possible functional and structural influence, therefore, could be used as genetic biomarkers and may assist in genetic studies with a special consideration of the large heterogeneity of AML.

• Acute myeloid leukemia
• CEBPA
• bioinformatics analysis
• genetic biomarkers
• malignant disease