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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http://dx.doi.org/10.1002/cam4.70326 | DOI Listing |
Histochem Cell Biol
January 2025
Department of Histology and Embryology, Faculty of Medicine, Ankara Yildirim Beyazit University, 06800, Ankara, Turkey.
Bone marrow mesenchymal stromal cells (BM-MSCs) are integral components of the bone marrow microenvironment, playing a crucial role in supporting hematopoiesis. Recent studies have investigated the potential involvement of BM-MSCs in the pathophysiology of acute lymphoblastic leukemia (ALL). However, the exact contribution of BM-MSCs to leukemia progression remains unclear because of conflicting findings and limited characterization.
View Article and Find Full Text PDFAnn Hematol
January 2025
Department of Hematology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Acute promyelocytic leukemia (APL) is driven by the specific fusion gene PML-RARA produced by chromosomal translocation. Three classic isoforms, L, V, and S, are found in more than 95% of APL patients. However, atypical PML-RARA isoforms are usually associated with uncertain disease progression and treatment prognosis.
View Article and Find Full Text PDFJ Cell Physiol
January 2025
Division of Hematology & Oncology, Department of Pediatrics, School of Medicine, Washington University in Saint Louis, St. Louis, Missouri, USA.
Fatty acids are essential biomolecules that support several cellular processes, such as membrane structures, energy storage and production, as well as signal transduction. Accordingly, changes in fatty acid metabolism can have a significant impact on cell behavior, such as growth, survival, proliferation, differentiation, and motility. Therefore, it is not surprising that many aspects of fatty acid metabolism are frequently dysregulated in human cancer, including in highly aggressive blood cancers such as acute leukemia.
View Article and Find Full Text PDFFront Oncol
January 2025
Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
Introduction: -rearrangements define a subclass of acute leukemias characterized by a distinct gene expression signature linked to the dysfunctional oncogenic fusion proteins arising from various chromosomal translocations involving the (also known as ) gene. Research on the disease pathomechanism in -rearranged acute leukemias has mainly focused on the upregulation of the stemness-related genes of the -family and their co-factor .
Results: Here we report the and fusion gene-dependent downregulation of , a TGF-β signaling axis transcription factor.
Front Oncol
January 2025
Department of Intensive Care Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Objective: Analyze the outcomes of critically ill patients who developed new-onset organ dysfunction and received systemic chemotherapy during their ICU stay.
Design: Retrospective cohort study.
Setting: A tertiary medical center in Germany with an Intensive Care Medicine department consists of 11 intensive care units comprising 140 beds, serving all subspecialties of adult intensive care medicine.
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