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

• Published in: Molecular biology reports Vol. 51; no. 1; p. 561
• Main Authors: Yu, Jinglei, Song, Fengmei, Zhang, Mingming, Xiao, Pingnan, Feng, Jingjing, Hong, Ruimin, Hu, Yongxian, Huang, He, Wei, Guoqing
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.12.2024; Springer Nature B.V
• Subjects: Acute lymphoblastic leukemia; Acute myeloid leukemia; Animal Anatomy; Animal Biochemistry; Biomedical and Life Sciences; Brief Report; Cbl protein; Chemoresistance; Chemotherapy; Chromosome 11; Chromosome deletion; Clinical outcomes; Disease Progression; Female; Gene rearrangement; Gene Rearrangement - genetics; Hematologic Neoplasms; Histology; Humans; Leukemia; Leukemia, Monocytic, Acute - genetics; Life Sciences; Lymphatic leukemia; Malignancy; Methyltransferase; Middle Aged; Morphology; Protein structure; Remission; KMT2A; Acute monoblastic leukemia; CBL; Acute myeloid leukemia
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-024-09543-0

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.