AI Article Synopsis

  • KMT2A rearrangements are common in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), leading to aggressive forms of leukemia with poor treatment responses.
  • This review consolidates research on KMT2A-r leukemia, covering its genetic traits, cytogenetics, clinical presentation, and potential treatment targets.
  • Future research focuses on understanding the biology of KMT2A-r leukemia and developing personalized, innovative therapies to improve patient outcomes.

Article Abstract

Background: Rearrangements of the histone-lysine-N-methyltransferase (KMT2A), previously referred to as mixed-lineage leukemia (MLL), are among the most common chromosomal abnormalities in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), involving numerous different fusion partners. KMT2A-rearranged (KMT2A-r) leukemia is characterized by a rapid onset, aggressive progression, and significantly worse prognosis compared to non-KMT2A-r leukemias. Even with contemporary chemotherapeutic treatments and hematopoietic stem cell transplantations (HSCT), patients with KMT2A-r leukemia typically experience poor outcomes and limited responses to these therapies.

Objectives: This review aims to consolidate recent studies on the general gene characteristics and associated mechanisms of KMT2A-r acute leukemia, as well as the cytogenetics, immunophenotype, clinical presentation, and risk stratification of both KMT2A-r-AML and KMT2A-r-ALL. Particularly, the treatment targets in KMT2A-r acute leukemia are examined.

Methods: A comprehensive review was carried out by systematically synthesizing existing literature on PubMed, using the combination of the keywords 'KMT2A-rearranged acute leukemia', 'lymphoblastic leukemia', 'myeloid leukemia', and 'therapy'. The available studies were screened for selection based on quality and relevance.

Conclusions: Studies indicate that KMT2A rearrangements are present in over 70% of infant leukemia cases, approximately 10% of adult AML cases, and numerous instances of secondary acute leukemias, making it a disease of critical concern to clinicians and researchers alike. The future of KMT2A-r acute leukemia research is characterized by an expanding knowledge of the disease's biology, with an emphasis on personalized therapies, immunotherapies, genomic advancements, and innovative therapeutic combinations. The overarching aim is to enhance patient outcomes, lessen the disease burden, and elevate the quality of life for those affected. Ongoing research and clinical trials in this area continue to offer promising opportunities for refining treatment strategies and improving patient prognosis.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491690PMC
http://dx.doi.org/10.1002/cam4.70326DOI Listing

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