Resistance to FLT3 inhibitors involves different molecular mechanisms and reduces new DNA synthesis.

ABSTRACT: Acute myeloid leukaemia (AML) is a hard to treat blood cancer. Mutations in FLT3 are common among the genetic aberrations that characterise the cancer. Patients initially react to FLT3 inhibitors but drug resistance is a hinder to successful therapy. To better understand the mechanisms leading to drug resistance, we generated four AML cell lines resistant to the inhibitors gilteritinib or FF-10101, and explored their resistance mechanisms. We further tested whether the novel inhibitor Chen-9u could be used to limit cell growth. The results showed that each of the four resistant cell lines became resistant through a different mechanism. Resistant cells showed decreased FLT3 and increased NRAS pathway activity and reduced DNA synthesis due to decrease in CDK4 activity. Resistance mechanisms

SUBMITTER: Yang J 

PROVIDER: S-EPMC11786753 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature