Published online Aug 24, 2020. doi: 10.5306/wjco.v11.i8.528
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
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.
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.