REPROGRAMMING OF SERINE METABOLISM IS A METABOLIC VULNERABILITY IN FMS-LIKE TYROSINE KINASE 3 (FLT3) MUTANT ACUTE MYELOID LEUKAEMIA

Abstract

Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene occur in approximately 30% of all acute myeloid leukaemias (AMLs) and are associated with poor prognosis. The clinical utility of FLT3 inhibitor monotherapy has been limited by the rapid development of resistance, highlighting the need for identification of alternative therapeutic targets for the treatment of FLT3-mutant AML. Using a syngeneic murine model of AML harbouring FLT3 internal tandem duplication (FLT3-ITD), we demonstrate that FLT3-ITD promotes serine uptake and serine synthesis via transcriptional regulation of neutral amino acid transporters (SLC1A4 and SLC1A5) and genes in the de novo serine synthesis pathway (PHGDH and PS..