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Increasing H3K9 methylation level reduces the proliferation of leukemic stem cells [bulk RNA-seq of IOX1-treated HM cells]

ABSTRACT: Genetic and epigenetic alterations accumulate throughout life in hematopoietic stem and progenitor cells (HSPCs), leading to an increased risk of age-related haematological malignancies such as acute myeloid leukaemia (AML). While a few epigenetic drugs have entered into clinical practice, studies focused on histone post-translational modifications (PTM) altered in AML remain limited. Here we used murine HSPCs, murine AML mouse models, human leukemic cell lines and leukemic patient samples to investigate whether targeting methylation of histone 3 at lysine 9 (H3K9 methylation) is affecting HSPCs upon aging and leukemogenesis and might represent a possible target. Our data shows that H3K9 methylation changes upon aging in HSPCs and is linked to a pre-malignant phenotype. Low levels of H3K9 methylation in leukemic cells are required to maintain proliferative capacities in vitro. Increasing H3K9 methylation reduces leukemogenesis of both young and aged murine and patient derived leukemic cells. Thus, H3K9 methylation might be a potential and selective therapeutic target in AML.

ORGANISM(S): Mus musculus

PROVIDER: GSE300249 | GEO | 2026/09/04

REPOSITORIES: GEO

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Increasing H3K9 methylation level reduces the proliferation of leukemic stem cells [bulk RNA-seq of H3R9 LSKs]

Project description:Genetic and epigenetic alterations accumulate throughout life in hematopoietic stem and progenitor cells (HSPCs), leading to an increased risk of age-related haematological malignancies such as acute myeloid leukaemia (AML). While a few epigenetic drugs have entered into clinical practice, studies focused on histone post-translational modifications (PTM) altered in AML remain limited. Here we used murine HSPCs, murine AML mouse models, human leukemic cell lines and leukemic patient samples to investigate whether targeting methylation of histone 3 at lysine 9 (H3K9 methylation) is affecting HSPCs upon aging and leukemogenesis and might represent a possible target. Our data shows that H3K9 methylation changes upon aging in HSPCs and is linked to a pre-malignant phenotype. Low levels of H3K9 methylation in leukemic cells are required to maintain proliferative capacities in vitro. Increasing H3K9 methylation reduces leukemogenesis of both young and aged murine and patient derived leukemic cells. Thus, H3K9 methylation might be a potential and selective therapeutic target in AML.

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