ACSL4-associated lipid metabolism is a distinct therapeutic vulnerability in KMT2A-rearranged acute myeloid leukemia - PubMed
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- #leukemia
- #lipid-metabolism
- #CRISPR
- ACSL4-associated lipid metabolism is a key vulnerability in KMT2A-rearranged AML.
- CRISPR-Cas9 screening identified ACSL4 as selectively essential for KMT2Ar AML cell growth.
- ACSL4 knockdown impaired colony formation in KMT2Ar AML cells and delayed leukemia in mice.
- Multi-omics analysis showed ACSL4 loss depletes polyunsaturated lipids and activates compensatory pathways.
- Exogenous PUFAs rescued growth defects, linking ACSL4 dependency to PUFA utilization.
- KRADS12 signature predicts poor survival in AML patients with KMT2Ar status.