Gilteritinib Inhibits Glutamine Uptake and Utilization in FLT3-ITD-Positive AML.

ABSTRACT: Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy associated with frequent relapse and poor overall survival. The tyrosine kinase inhibitor gilteritinib is approved for the treatment of relapse/refractory AML with FLT3 mutations, yet its mechanism of action is not completely understood. Here, we sought to identify additional therapeutic targets that can be exploited to enhance gilteritinib's antileukemic effect. Based on unbiased transcriptomic analyses, we identified the glutamine transporter SNAT1 (SLC38A1) as a novel target of gilteritinib that leads to impaired glutamine uptake and utilization within leukemic cells. Using metabolomics and metabolic flux analyses, we found that gilteriti

SUBMITTER: Zavorka Thomas ME 

PROVIDER: S-EPMC8687141 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature