Targeting FLT3-TAZ signaling to suppress drug resistance in blast phase chronic myeloid leukemia.

ABSTRACT:

Background

Although the development of BCR::ABL1 tyrosine kinase inhibitors (TKIs) rendered chronic myeloid leukemia (CML) a manageable condition, acquisition of drug resistance during blast phase (BP) progression remains a critical challenge. Here, we reposition FLT3, one of the most frequently mutated drivers of acute myeloid leukemia (AML), as a prognostic marker and therapeutic target of BP-CML.

Methods

We generated FLT3 expressing BCR::ABL1 TKI-resistant CML cells and enrolled phase-specific CML patient cohort to obtain unpaired and paired serial specimens and verify the role of FLT3 signaling in BP-CML patients. We performed multi-omics approaches in animal and patient studies to demonstrate the clinical feasibility of FLT3 as a viable target of BP-CML by establishing

SUBMITTER: Shin JE 

PROVIDER: S-EPMC10626670 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature