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Current Hematologic Malignancy Reports

, Volume 13, Issue 4, pp 256–264 | Cite as

Shutting Down Acute Myeloid Leukemia and Myelodysplastic Syndrome with BCL-2 Family Protein Inhibition

  • Prashant Sharma
  • Daniel A Pollyea
Myelodysplastic Syndromes (M Savona, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Myelodysplastic Syndromes

Abstract

Purpose of Review

Apoptosis results from the interaction between pro- and anti-apoptotic proteins, mediated by BCL-2 homology 3 (BH3) proteins. B cell lymphoma-2 (BCL-2) is an inhibitor of apoptosis which stabilizes the mitochondria, resulting in the prevention of activation of the pro-apoptotic proteins. In addition, BCL-2 is overexpressed in the leukemic stem cell (LSC) population, and its inhibition may lead to selective LSC eradication. Herein, we will discuss the mechanism and rationale of BCL-2 inhibition in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with an overview of the selective BCL-2 inhibitor venetoclax.

Recent Findings

Venetoclax has activity against AML and has displayed synergistic activity with hypomethylating agents in the preclinical setting. In the clinical setting, although it has only modest activity as a single agent in relapsed and refractory AML, in the older, treatment-naïve population, in combination with either a hypomethylator or low-dose cytarabine, it is well tolerated with impressive efficacy. In addition, BCL-2 inhibition may also have activity in MDS, and although clinical trials are in their early phases, this may be an effective strategy in both the up-front and relapsed setting.

Summary

BCL-2 inhibition with venetoclax is well tolerated and active in older patients with newly diagnosed AML and in the relapsed setting has activity that may be improved in combination with other therapies. It may prove to be effective in MDS and is an exciting treatment strategy for myeloid malignancies.

Keywords

BCL-2 Acute myeloid leukemia Myelodysplastic syndrome AML MDS Apoptosis Venetoclax 

Notes

Compliance with Ethical Standards

Conflict of Interest

Daniel A Pollyea served as an advisory board member for Celyad, Agios, Celgene, Abbvie, Argenx, Pfizer, Curis, Takeda, and Servier, and received research funding from Agios and Pfizer. Prashant Sharma declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. 1.Division of HematologyUniversity of Colorado School of MedicineAuroraUSA

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