Non-genetic mechanisms of drug resistance in acute leukemias.

Document Type

Article

Publication Date

1-1-2024

Keywords

JGM, Humans, Leukemia, Myeloid, Acute, Recurrence, Drug Resistance

JAX Source

Trends Cancer. 2024;10(1):38-51.

ISSN

2405-8025

PMID

37839973

DOI

https://doi.org/10.1016/j.trecan.2023.09.003

Grant

This work was supported by The Jackson Laboratory and JAX start-up funds.

Abstract

Acute leukemia is characterized by clonal heterogeneity that contributes to poor drug responses in patients. Despite treatment advances, the occurrence of relapse remains a major barrier to achieving cures as current therapeutic approaches are inadequate to effectively prevent or overcome resistance. Given that only a few genetic mutations are associated with relapse in acute leukemia patients, there is a growing focus on 'non-genetic' mechanisms that affect the hallmarks of cancer to allow leukemic cells to survive post therapy. In this review, we provide an overview of the therapeutic landscape in acute leukemias. Importantly, we discuss non-genetic mechanisms exploited by leukemic cells to promote their survival after treatment. Last, we present current strategies to prevent or overcome drug resistance in this disease.

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