A rare KMT2A::CBL transcript in an acute monoblastic leukemia patient with an unfavorable outcome

Mol Biol Rep. 2024 Apr 21;51(1):561. doi: 10.1007/s11033-024-09543-0.

Abstract

Background: Lysine [K] methyltransferase 2A (KMT2A, previously known as MLL) gene rearrangements are common in acute leukemias of various lineages and are associated with features such as chemotherapy resistance and rapid relapse. KMT2A::CBL is a rare fusion of unknown pathogenesis generated by a unique interstitial deletion of chromosome 11 that has been reported across a wide age range in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. The leukemogenic effect of the KMT2A::CBL rearrangement and its association with clinical prognosis have not been well clarified.

Methods and results: We report the case of a 64-year-old female who was diagnosed with acute monoblastic leukemia (M5a) and who acquired the rare KMT2A::CBL fusion. The patient received multiple cycles of therapy but did not achieve remission and eventually succumbed to severe infection and disease progression. Additionally, we characterized the predicted KMT2A-CBL protein structure in this case to reveal the underlying leukemogenic mechanisms and summarized reported cases of hematological malignancies with KMT2A::CBL fusion to investigate the correlation of gene rearrangements with clinical outcomes.

Conclusions: This report provides novel insights into the leukemogenic potential of the KMT2A::CBL rearrangement and the correlation between gene rearrangements and clinical outcomes.

Keywords: Acute monoblastic leukemia; Acute myeloid leukemia; CBL; KMT2A.

Publication types

  • Case Reports

MeSH terms

  • Disease Progression
  • Female
  • Gene Rearrangement / genetics
  • Histone-Lysine N-Methyltransferase* / genetics
  • Humans
  • Leukemia, Monocytic, Acute* / genetics
  • Leukemia, Monocytic, Acute* / pathology
  • Middle Aged
  • Myeloid-Lymphoid Leukemia Protein* / genetics
  • Proto-Oncogene Proteins c-cbl* / genetics

Substances

  • KMT2A protein, human
  • Histone-Lysine N-Methyltransferase
  • Myeloid-Lymphoid Leukemia Protein
  • CBL protein, human
  • Proto-Oncogene Proteins c-cbl