KF1601, a dual inhibitor of BCR::ABL1 and FLT3, overcomes drug resistance in FLT3⁺ blast phase chronic myeloid leukemia.

ABSTRACT: Blast phase chronic myeloid leukemia (BP-CML) poses significant clinical challenges due to its drug resistance, resulting from BCR::ABL1-dependent mutations and BCR::ABL1-independent pathways. Previously, we reported that FLT3 pathway is activated in ~ 50% of BP-CML cases, indicating a potential avenue for therapeutic intervention via dual inhibition of BCR::ABL1 and FLT3. Here, we aimed to evaluate the efficacy of KF1601, a dual inhibitor of BCR::ABL1 and FLT3, in overcoming drug resistance in BP-CML while also comparing its thrombo-inflammatory responses with those of ponatinib, known to have severe cardiovascular adverse events in human. Our findings revealed that KF1601 effectively inhibited of BCR::ABL1 signaling pathway, even in the presence of the T315I mutation. KF1601 achieved com

SUBMITTER: Kwon HJ 

PROVIDER: S-EPMC11995503 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature