ArticleHaematologica2022
Epigenetic changes in human model KMT2A leukemias highlight early events during leukemogenesis.
Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Molecular Landscape of Acute Myeloid Leukemia in Pediatric Patient-Age-Related Correlations: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Epigenetics and In Silico Transcriptome Analysis of Pediatric Acute Myeloid Leukemia.European journal of haematology · 2026Review
- Prognostic impact of KMT2A-PTD in acute myeloid leukemia in the NGS era: a multicenter retrospective study.Annals of hematology · 2026Observational
- The nutrigenomic-epigenetic axis in cancer: from dietary bioactives to precision oncology.Nutrition & metabolism · 2026Review
- A Rare Case of De Novo Acute Myeloid Leukemia, Featuring aDiagnostics (Basel, Switzerland) · 2026Article
- Acute leukemia of ambiguous lineage: the known and the uncertain.Haematologica · 2026Review
- Review
- CharacterizingCancers · 2026Article
- Characteristics and outcomes of newly diagnosed acute myeloid Leukemia with KMT2A rearrangements.Leukemia · 2025Article
- Epigenomics and transcriptomics association study of blood pressure and incident diagnosis of hypertension in twins.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- Fusion Genes in Myeloid Malignancies.Cancers · 2024Review
- The epigenetic regulators EP300/CREBBP represent promising therapeutic targets in MLL-rearranged acute myeloid leukemia.Cell death discovery · 2024Article
- Mapping AML heterogeneity - multi-cohort transcriptomic analysis identifies novel clusters and divergent ex-vivo drug responses.Leukemia · 2024Article
- Alternative splicing generates isoform diversity inEndocrine oncology (Bristol, England) · 2024Article
- Stem-Cell Aging and Pathways to Precancer Evolution.The New England journal of medicine · 2023Review
- Bone Marrow Microenvironment-Induced Chemoprotection inCancers · 2023Article
- Advances in molecular characterization of pediatric acute megakaryoblastic leukemia not associated with Down syndrome; impact on therapy development.Frontiers in cell and developmental biology · 2023Review
- Inflammatory bone marrow signaling in pediatric acute myeloid leukemia distinguishes patients with poor outcomes.Nature communications · 2022Article
- Increasing Complexity of Molecular Landscapes in Human Hematopoietic Stem and Progenitor Cells during Development and Aging.International journal of molecular sciences · 2022Review
- The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies.Biomolecules · 2021Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chromosomal translocations involving KMT2A gene are one of the most common genetic alterations found in pediatric acute myeloid leukemias (AML) although the molecular mechanisms that initiate the disease remain incompletely defined. To elucidate these initiating events we have used a human model system of AML driven by the KMT2A-MLLT3 (KM3) fusion. More specifically, we investigated changes in DNA methylation, histone modifications, and chromatin accessibility at each stage of our model system and correlated these with expression changes. We observe the development of a profound hypomethylation phenotype in the early stages of leukemic transformation after KM3 addition along with loss of expression of stem cell associated genes along with skewed expression in other genes such as S100A8/9 implicated in leukemogenesis. In addition, early increases in the expression of the lysine demethylase KDM4B was functionally linked to these expression changes as well as other key transcription factors. Remarkably, our ATAC-seq data showed that there were relatively few leukemiaspecific changes and the vast majority corresponded to open chromatin regions and transcription factor clusters previously observed in other cell types. Integration of the gene expression and epigenetic changes revealed the adenylate cyclase gene ADCY9 as an essential gene in KM3-AML, and suggest the potential for autocrine signalling through the chemokine receptor CCR1 and CCL23 ligand. Together, our results suggest that KM3 induces subtle changes in the epigenome while co-opting the normal transcriptional machinery to drive leukemogenesis.
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