Dasatinib overcomes AML cells resistant to BCL2 inhibition by degrading MCL1.

ABSTRACT: Acute myeloid leukaemia (AML) is a severe disease occurring mainly in the elderly population. Venetoclax (VEN) combined with azacitidine has changed the paradigm of treatment of AML. Nevertheless, approximately 30% of patients are primary refractory to VEN (VEN-R), with no current therapeutic option. To target VEN-R AML, we collected primary blasts at AML diagnosis in a prospective biobanking trial (NCT02320656). We performed targeted Next Generation Sequencing and ex vivo drug testing in 108 AML samples. We noticed that 17 (15.7%) were navitoclax-resistant (NAV-R). We observed a strong anticorrelation between NAV and Dasatinib (DASA) ex vivo sensitivity, also found in the BEAT-AML cohort. As NAV and ABT797 are both BCL2/BCLxL inhibitors, we hypothesized that blasts sensitive to DASA (DASA

SUBMITTER: Garciaz S 

PROVIDER: S-EPMC12378904 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature