KMT2A Rearrangements in Leukemias: Molecular Aspects and Therapeutic Perspectives.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Myeloid-Lymphoid Leukemia Protein*/genetics ; Histone-Lysine N-Methyltransferase*/genetics ; Gene Rearrangement* ; Leukemia*/genetics ; Leukemia*/therapy; Humans ; Hematopoietic Stem Cell Transplantation ; Translocation, Genetic

KMT2A (alias: mixed-lineage leukemia [ MLL ]) gene mapping on chromosome 11q23 encodes the lysine-specific histone N-methyltransferase 2A and promotes transcription by inducing an open chromatin conformation. Numerous genomic breakpoints within the KMT2A gene have been reported in young children and adults with hematologic disorders and are present in up to 10% of acute leukemias. These rearrangements describe distinct features and worse prognosis depending on the fusion partner, characterized by chemotherapy resistance and high rates of relapse, with a progression-free survival of 30-40% and overall survival below 25%. Less intensive regimens are used in pediatric patients, while new combination therapies and targeted immunotherapeutic agents are being explored in adults. Beneficial therapeutic effects, and even cure, can be reached with hematopoietic stem cell transplantation, mainly in young children with dismal molecular lesions; however, delayed related toxicities represent a concern. Herein, we summarize the translocation partner genes and partial tandem duplications of the KMT2A gene, their molecular impact, clinical aspects, and novel targeted therapies.

Erratum in: Int J Mol Sci. 2024 Nov 01;25(21):11743. doi: 10.3390/ijms252111743. (PMID: 39519407)

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Keywords: KMT2A rearrangements; molecular lesions; therapies

149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
0 (KMT2A protein, human)

Date Created: 20240829 Date Completed: 20240829 Latest Revision: 20241109

20250114

PMC11354696

10.3390/ijms25169023

39201709