ArticleBlood2020
SETD2 deficiency accelerates MDS-associated leukemogenesis via S100a9 in NHD13 mice and predicts poor prognosis in MDS.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
- Genomic Characterization of Epigenetic Regulator Gene Alterations in Juvenile Myelomonocytic Leukemia Through Whole-Exome Sequencing.Epigenomes · 2026Article
- Deficiency of Setd2 in mesenchymal stem cells facilitates the progression of myelodysplastic syndrome to leukemia.Molecular medicine (Cambridge, Mass.) · 2026Article
- Aberrant Kupffer-like differentiation of hematopoietic stem cell is critical for the MDS pathogenesis in Setd2-deficient mice.Cell death and differentiation · 2026Article
- SETD2 inhibited T-cell acute lymphocytic leukemia invasion and infiltration by inhibiting the JAK/STAT pathway.Molecular and cellular biochemistry · 2026Article
- Loss of SETD2-mediated H3K36me3 Drives CD8Research (Washington, D.C.) · 2026Article
- Base-resolution DNA methylome of human MDS hematopoietic stem cell reveals TET2-GFI1 epigenetic axis repressing MDS.Immunity & inflammation · 2026Article
- Co-operative epigenetic remodelling by Setd2 deficiency and Kras mutation drives juvenile myelomonocytic leukaemia development and MEK inhibitor sensitivity.British journal of haematology · 2025Article
- Non-essential role of S100A9 in hematopoiesis in primary MPN and MDS mouse models.Cancer biology & medicine · 2025Article
- Single-cell transcriptome sequencing reveals the mechanism of Realgar improvement on erythropoiesis in mice with myelodysplastic syndrome.Cancer cell international · 2025Article
- Catalytic activity of Setd2 is essential for embryonic development in mice: establishment of a mouse model harboring patient-derived Setd2 mutation.Frontiers of medicine · 2024Article
- SETD2 in cancer: functions, molecular mechanisms, and therapeutic regimens.Cancer biology & medicine · 2024Article
- Bone marrow inflammation in haematological malignancies.Nature reviews. Immunology · 2024Review
- Prognostic and therapeutic roles ofAging · 2024Article
- Histone methyltransferase SETD2 is required for proper hippocampal lamination and neuronal maturation.Molecular biology of the cell · 2024Article
- Single-cell transcriptomic profiling reveals immune cell heterogeneity in acute myeloid leukaemia peripheral blood mononuclear cells after chemotherapy.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Article
- ABIN1 (Q478) is Required to Prevent Hematopoietic Deficiencies through Regulating Type I IFNs Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Tumor-suppressive functions of protein lysine methyltransferases.Experimental & molecular medicine · 2023Review
- KMT2D Deficiency Promotes Myeloid Leukemias which Is Vulnerable to Ribosome Biogenesis Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
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Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
Abstract
SETD2, the histone H3 lysine 36 methyltransferase, previously identified by us, plays an important role in the pathogenesis of hematologic malignancies, but its role in myelodysplastic syndromes (MDSs) has been unclear. In this study, low expression of SETD2 correlated with shortened survival in patients with MDS, and the SETD2 levels in CD34+ bone marrow cells of those patients were increased by decitabine. We knocked out Setd2 in NUP98-HOXD13 (NHD13) transgenic mice, which phenocopies human MDS, and found that loss of Setd2 accelerated the transformation of MDS into acute myeloid leukemia (AML). Loss of Setd2 enhanced the ability of NHD13+ hematopoietic stem and progenitor cells (HSPCs) to self-renew, with increased symmetric self-renewal division and decreased differentiation and cell death. The growth of MDS-associated leukemia cells was inhibited though increasing the H3K36me3 level by using epigenetic modifying drugs. Furthermore, Setd2 deficiency upregulated hematopoietic stem cell signaling and downregulated myeloid differentiation pathways in the NHD13+ HSPCs. Our RNA-seq and chromatin immunoprecipitation-seq analysis indicated that S100a9, the S100 calcium-binding protein, is a target gene of Setd2 and that the addition of recombinant S100a9 weakens the effect of Setd2 deficiency in the NHD13+ HSPCs. In contrast, downregulation of S100a9 leads to decreases of its downstream targets, including Ikba and Jnk, which influence the self-renewal and differentiation of HSPCs. Therefore, our results demonstrated that SETD2 deficiency predicts poor prognosis in MDS and promotes the transformation of MDS into AML, which provides a potential therapeutic target for MDS-associated acute leukemia.
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