S1P Receptor Modulation Restores FLT3 Inhibitor Sensitivity in NRAS-Mutated FLT3-ITD Acute Myeloid Leukemia

Highlights

FLT3 inhibitor resistance in FLT3-ITD acute myeloid leukemia frequently emerges through acquired RAS-pathway mutations, particularly NRAS, creating a major barrier to durable disease control.

In this preclinical study, the clinically available sphingosine-1-phosphate receptor modulators fingolimod (FTY720) and mocravimod (KRP-203) restored sensitivity to FLT3 inhibition in multiple NRAS-mutated FLT3-ITD AML models, including primary patient blasts.

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