Non-genetic mechanisms of drug resistance in acute leukemias

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.