ArticleBlood advances2019
Critical role of Jumonji domain of JMJD1C in MLL-rearranged leukemia.
Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Article
- Diving into the transcriptional landscape of leukemic stem cells in acute myeloid leukemia at single-cell resolution.Journal of cancer research and clinical oncology · 2026Review
- Proteomics landscape of early T-cell precursor acute lymphoblastic leukemia reveals deficient oxidative phosphorylation signatures.Cell reports. Medicine · 2026Article
- JMJD1C forms condensate to facilitate a RUNX1-dependent gene expression program shared by multiple types of AML cells.Protein & cell · 2025Article
- Impact of Tyrosine Kinase Inhibitors on the Expression Pattern of Epigenetic Regulators.Cancers · 2025Article
- Review
- Epigenetic roles of KDM3B and KDM3C in tumorigenesis and their therapeutic implications.Cell death & disease · 2024Review
- The emerging roles of histone demethylases in cancers.Cancer metastasis reviews · 2024Review
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- The Importance of M1-and M2-Polarized Macrophages in Glioma and as Potential Treatment Targets.Brain sciences · 2023Review
- Interrogating bromodomain inhibitor resistance in KMT2A-rearranged leukemia through combinatorial CRISPR screens.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Bioinformatic Analyses of Broad H3K79me2 Domains in Different Leukemia Cell Line Data Sets.Cells · 2022Article
- The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies.Biomolecules · 2021Review
- Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia.Nature genetics · 2021Article
- AR-negative prostate cancer is vulnerable to loss of JMJD1C demethylase.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Histone demethylase JMJD1C promotes the polarization of M1 macrophages to prevent glioma by upregulating miR-302a.Clinical and translational medicine · 2021Article
- A chromatin perspective on metabolic and genotoxic impacts on hematopoietic stem and progenitor cells.Cellular and molecular life sciences : CMLS · 2020Review
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Authors and funding
13 authors.
Funding
Abstract
JMJD1C, a member of the lysine demethylase 3 family, is aberrantly expressed in mixed lineage leukemia (MLL) gene-rearranged (MLLr) leukemias. We have shown previously that JMJD1C is required for self-renewal of acute myeloid leukemia (AML) leukemia stem cells (LSCs) but not normal hematopoietic stem cells. However, the domains within JMJD1C that promote LSC self-renewal are unknown. Here, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) negative-selection screening and identified a requirement for the catalytic Jumonji (JmjC) domain and zinc finger domain for leukemia cell survival in vitro and in vivo. In addition, we found that histone H3 lysine 36 methylation (H3K36me) is a marker for JMJD1C activity at gene loci. Moreover, we performed single cell transcriptome analysis of mouse leukemia cells harboring a single guide RNA (sgRNA) against the JmjC domain and identified increased activation of RAS/MAPK and the JAK-STAT pathway in cells harboring the JmjC sgRNA. We discovered that upregulation of interleukin 3 (IL-3) receptor genes mediates increased activation of IL-3 signaling upon JMJD1C loss or mutation. Along these lines, we observed resistance to JMJD1C loss in MLLr AML bearing activating RAS mutations, suggesting that RAS pathway activation confers resistance to JMJD1C loss. Overall, we discovered the functional importance of the JMJD1C JmjC domain in AML leukemogenesis and a novel interplay between JMJD1C and the IL-3 signaling pathway as a potential resistance mechanism to targeting JMJD1C catalytic activity.
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