A GENETIC variant, the BIM deletion polymorphism (BDP), has been identified by researchers to significantly enhance leukemia stem and progenitor cells’ survival, making them resistant to common targeted therapies. This discovery could influence treatment strategies for chronic myeloid leukemia (CML) and related cancers.
The study, conducted using a humanized mouse model, focused on understanding BDP’s impact on leukemia cells’ response to treatment. Findings revealed that cells with the BDP variant show nearly complete resistance to apoptosis, programmed cell death, when exposed to imatinib, a standard therapy for CML. By altering the cells’ internal BCL-2 pathway, BDP essentially rewires leukemia cells to survive against drugs designed to destroy them.
Results indicate that leukemia cells with BDP exhibit a three-fold competitive advantage, leading to faster disease progression and higher relapse risk. However, this study also identified a potential pathway to overcome BDP-induced resistance: MCL-1 inhibitors. Researchers demonstrated that these inhibitors effectively targeted BDP-positive leukemia stem cells in both animal and human models, suggesting new treatment avenues for resistant forms of leukemia.
Experts suggest that screening for the BIM deletion polymorphism could soon become integral to personalized leukemia treatment, helping identify patients who may benefit from alternative or combination therapies to overcome drug resistance.
Reference: Yu M et al. The BIM deletion polymorphism potentiates the survival of leukemia stem and progenitor cells and impairs response to targeted therapies. 2024.
