Glutamine-dependent downregulation of FLT3-ITD is a mechanism of FLT3 inhibitor resistance in FLT3-ITD AML in hypoxia

FLT3 inhibitors have improved outcomes in acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), but responses are not durable. Notably, FLT3 inhibitors clear blasts from the blood, but not the bone marrow, a hypoxic niche. We investigated effects of hypoxia and the key nutrient glutamine on FLT3 inhibitor response. FLT3-ITD AML cell lines and patient blasts were cultured with FLT3 inhibitors under normoxia (21%) or hypoxia ( View larger version (52K): org.highwire.dtl.DTLVardef@1746bf8org.highwire.dtl.DTLVardef@5c9cdeorg.highwire.dtl.DTLVardef@3ee12aorg.highwire.dtl.DTLVardef@30c90c_HPS_FORMAT_FIGEXP M_FIG C_FIG