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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Aug 24, 2020; 11(8): 528-540
Published online Aug 24, 2020. doi: 10.5306/wjco.v11.i8.528
B-cell lymphoma-2 inhibition and resistance in acute myeloid leukemia
Lindsay Wilde, Sabarina Ramanathan, Margaret Kasner
Lindsay Wilde, Sabarina Ramanathan, Margaret Kasner, Department of Hematology and Medical Oncology, Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital, Philadelphia, PA 19107, United States
Author contributions: Wilde L and Ramanathan S prepared the first draft of the article; Kasner M contributed to reviewing and revising the manuscript; Wilde L led the coordination in preparing the manuscript.
Conflict-of-interest statement: Kasner M reports grants and personal fees from Jazz, grants and personal fees from Daiichi, grants from Roche, grants and personal fees from Atellas, grants from Pfizer, grants and personal fees from Otsuka, grants and personal fees from ONO, outside the submitted work.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Margaret Kasner, MD, MSc, Associate Professor, Department of Hematology and Medical Oncology, Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital, 834 Chestnut Street Suite 315, Philadelphia, PA 19107, United States. margaret.kasner@jefferson.edu
Received: January 3, 2020
Peer-review started: January 3, 2020
First decision: April 3, 2020
Revised: July 1, 2020
Accepted: July 19, 2020
Article in press: July 19, 2020
Published online: August 24, 2020
Abstract

Spurred by better understanding of disease biology, improvements in molecular diagnostics, and the development of targeted therapies, the treatment of acute myeloid leukemia (AML) has undergone significant evolution in recent years. Arguably, the most exciting shift has come from the success of treatment with the B-cell lymphoma-2 inhibitor venetoclax. When given in combination with a hypomethylating agent or low dose cytarabine, venetoclax demonstrates high response rates, some of which are durable. In spite of this, relapses after venetoclax treatment are common, and much interest exists in elucidating the mechanisms of resistance to the drug. Alterations in leukemic stem cell metabolism have been identified as a possible escape route, and clinical trials focusing on targeting metabolism in AML are ongoing. This review article highlights current research regarding venetoclax treatment and resistance in AML with a focus on cellular metabolism.

Keywords: Acute myeloid leukemia, B-cell lymphoma-2, Venetoclax, Metabolism, Leukemic stem cell, Resistance

Core tip: The B-cell lymphoma-2 inhibitor venetoclax has drastically changed the treatment paradigm for acute myeloid leukemia; however, much is unknown about mechanisms of relapse after treatment with this agent. Alterations in cellular metabolism have been identified as a potential resistance mechanism and may be able to be targeted with novel treatments.