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@ARTICLE{Schfer:309982,
      author       = {S. Schäfer and E. Rahimian and L. Schmitz-Hübsch and M.
                      Shaikh and S. Brilloff and V. Kufrin and S. Küchler and M.
                      Fedorova and N. Kusebauch and Z. Ni and D. Helm$^*$ and I.
                      Jeremias and D. M. Schewe and C. R. Ball and M. Bornhäuser
                      and H. Glimm$^*$ and M. Alberich-Jorda and M. Bill$^*$ and
                      A. A. Wurm$^*$},
      title        = {{ACSL}4-associated lipid metabolism is a distinct
                      therapeutic vulnerability in {KMT}2{A}-rearranged acute
                      myeloid leukemia.},
      journal      = {Cell reports},
      volume       = {45},
      number       = {3},
      issn         = {2211-1247},
      address      = {Maryland Heights, MO},
      publisher    = {Cell Press},
      reportid     = {DKFZ-2026-00408},
      pages        = {117010},
      year         = {2026},
      abstract     = {Deregulated lipid metabolism contributes to leukemogenesis
                      and the progression of acute myeloid leukemia (AML). By
                      analyzing large-scale CRISPR-Cas9 screening data, we
                      identified acyl-CoA synthetase long-chain family member 4
                      (ACSL4) as a selective vulnerability in lysine
                      methyltransferase 2A-rearranged (KMT2Ar) AML. Functional
                      validation using CRISPR interference and short hairpin RNA
                      knockdown confirmed that ACSL4 loss impairs the growth of
                      KMT2Ar but not non-KMT2Ar AML cells. ACSL4 knockdown reduced
                      colony formation in cells derived from patients with KMT2Ar
                      AML and murine MLL-AF9 cells and delayed leukemia onset in
                      vivo in MLL-AF9 mice. A multi-omics approach, including
                      transcriptomics, proteomics, and lipidomics, revealed
                      depletion of polyunsaturated lipid species and compensatory
                      activation of lipid metabolic pathways upon ACSL4 loss.
                      Supplementation with exogenous polyunsaturated fatty acids
                      (PUFAs) rescued the growth defect, linking ACSL4 dependency
                      to defective PUFA utilization. Finally, we generated a
                      KMT2Ar-ACSL4 dependency signature (KRADS12) that correlates
                      with KMT2Ar status and predicts poor survival in patients
                      with AML.},
      keywords     = {CP: cancer (Other) / CP: metabolism (Other) / acute myeloid
                      leukemia (Other) / chromosomal rearrangements (Other) /
                      lipid metabolism (Other)},
      cin          = {W120 / DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)W120-20160331 / I:(DE-He78)DD01-20160331},
      pnm          = {319H - Addenda (POF4-319H)},
      pid          = {G:(DE-HGF)POF4-319H},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41712378},
      doi          = {10.1016/j.celrep.2026.117010},
      url          = {https://inrepo02.dkfz.de/record/309982},
}