Venetoclax plus gilteritinib is effective in preclinical models of FLT3-mutant BCL11B-a lineage-ambiguous leukemia.

ABSTRACT: Aberrant activation of BCL11B ("BCL11B-a") defines a subtype of lineage ambiguous leukemias with T-lymphoid and myeloid features, co-occurring activating FLT3 mutations, and a stem/progenitor immunophenotype and gene expression profile. As with other lineage ambiguous leukemias, optimal treatment is unclear and there are limited targeted therapeutic options. Here, we investigated the efficacy of BCL-2 and FLT3 inhibition with venetoclax and gilteritinib, respectively, in preclinical models of BCL11B-a leukemia. Despite variation in response to single agent therapies, the combination of venetoclax plus gilteritinib (VenGilt) was highly effective in all models evaluated. BH3 profiling suggested that resistance to venetoclax monotherapy was due to the tumor-intrinsic dependence on additional

SUBMITTER: Montefiori LE 

PROVIDER: S-EPMC12377505 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature