Targeting Apoptosis in AML: Where Do We Stand?

Abstract

Simple SummaryIn patients with acute myeloid leukemia (AML), genetic mutations can cause cells to evade regulated cell death (RCD), resulting in excessive cell proliferation. The best-known form of RCD is apoptosis, which prevents the emergence of cancer cells; disturbances in this process are an important factor in the development and progression of AML. Clearly, it is essential to understand the mechanisms of apoptosis to establish a personalized, patient-specific approach in AML therapy. Therefore, this paper comprehensively reviews the current range of AML treatment approaches related to apoptosis and highlights other promising concepts such as neddylation.More than 97% of patients with acute myeloid leukemia (AML) demonstrate genetic mutations leading to excessive proliferation combined with the evasion of regulated cell death (RCD). The most prominent and well-defined form of RCD is apoptosis, which serves as a defense mechanism against the emergence of cancer cells. Apoptosis is regulated in part by the BCL-2 family of pro- and anti-apoptotic proteins, whose balance can significantly determine cell survival. Apoptosis evasion plays a key role in tumorigenesis and drug resistance, and thus in the development and progression of AML. Research on the structural and biochemical aspects of apoptosis proteins and their regulators offers promise for new classes of targeted therapies and strategies for therapeutic intervention. This review provides a comprehensive overview of current AML treatment options related to the mechanism of apoptosis, particularly its mitochondrial pathway, and other promising concepts such as neddylation. It pays particular attention to clinically-relevant aspects of current and future AML treatment approaches, highlighting the molecular basis of individual therapies.