Journal article

Reprogramming of serine metabolism is an actionable vulnerability in FLT3-ITD driven acute myeloid leukaemia

Stefan Bjelosevic, Emily Gruber, Andrea Newbold, Lev Kats, Carolyn Shembrey, Thomas Abrehart, Izabela Todorovski, Giovanna Pomilio, Andrew Wei, Gareth Gregory, Stephin Vervoort, Kristin Brown, Ricky Johnstone

Published : 2020

Abstract

Activating FMS-like tyrosine kinase 3 ( FLT3 ) mutations occur in approximately 30% of all acute myeloid leukaemias (AMLs) and are associated with poor prognosis. The limited clinical efficacy of FLT3 inhibitor monotherapy has highlighted the need for alternative therapeutic targets and treatments for FLT3-mutant AML. Using human and murine models of MLL-rearranged AML harbouring FLT3 internal tandem duplication (FLT3-ITD) and primary patient samples, we have demonstrated 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 PSAT1 ). Mechan..

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