ArticleEBioMedicine2020
Chronic myelomonocytic leukaemia stem cell transcriptomes anticipate disease morphology and outcome.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
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- Epigenetic programming by H3K23ac defines lineage fate of Meg3Nature cell biology · 2026Article
- A unique malignant cell type per patient tumor encoded in each cancer cell transcriptome.iScience · 2026Article
- Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencing.Chinese medical journal · 2025Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Pathway analysis through mutual information.Bioinformatics (Oxford, England) · 2024Article
- Application and research progress of single cell sequencing technology in leukemia.Frontiers in oncology · 2024Review
- Early activation of inflammatory pathways in UBA1-mutated hematopoietic stem and progenitor cells in VEXAS.Cell reports. Medicine · 2023Article
- The effects of MYC on tumor immunity and immunotherapy.Cell death discovery · 2023Review
- Progenitor Hierarchy of Chronic Myelomonocytic Leukemia Identifies Inflammatory Monocytic-Biased Trajectory Linked to Worse Outcomes.Blood cancer discovery · 2022Article
- Pregnancy exposure to synthetic phenols and placental DNA methylation - An epigenome-wide association study in male infants from the EDEN cohort.Environmental pollution (Barking, Essex : 1987) · 2021Article
- Increasing recognition and emerging therapies argue for dedicated clinical trials in chronic myelomonocytic leukemia.Leukemia · 2021Review
- Single-cell RNA sequencing in cancer: Applications, advances, and emerging challenges.Molecular therapy oncolytics · 2021Review
- The delta isoform of phosphatidylinositol-3-kinase predominates in chronic myelomonocytic leukemia and can be targeted effectively with umbralisib and ruxolitinib.Experimental hematology · 2021Article
- Inflammatory Regulation by TNF-α-Activated Adipose-Derived Stem Cells in the Human Bladder Cancer Microenvironment.International journal of molecular sciences · 2021Article
- Natural Barcodes for Longitudinal Single Cell Tracking of Leukemic and Immune Cell Dynamics.Frontiers in immunology · 2021Review
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7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundChronic myelomonocytic leukaemia (CMML) is a clinically heterogeneous stem cell malignancy with overlapping features of myelodysplasia and myeloproliferation. Over 90% of patients carry mutations in epigenetic and/or splicing genes, typically detectable in the Lin
methodsWe performed single-cell RNA sequencing on 6826 Lin
findingsWe found substantial inter- and intra-patient heterogeneity, with CMML stem cells displaying distinctive transcriptional programs. Compared with normal controls, CMML stem cells exhibited transcriptomes characterized by increased expression of myeloid-lineage and cell cycle genes, and lower expression of genes selectively expressed by normal haematopoietic stem cells. Neutrophil-primed progenitor genes and a MYC transcription factor regulome were prominent in stem cells from CMML-1 patients, whereas CMML-2 stem cells exhibited strong expression of interferon-regulatory factor regulomes, including those associated with IRF1, IRF7 and IRF8. CMML-1 and CMML-2 stem cells (stages distinguished by proportion of downstream blasts and promonocytes) differed substantially in both transcriptome and pseudotime, indicating fundamentally different biology underpinning these disease states. Gene expression and pathway analyses highlighted potentially tractable therapeutic vulnerabilities for downstream investigation. Importantly, CMML patients harboured variably-sized subpopulations of transcriptionally normal stem cells, indicating a potential reservoir to restore functional haematopoiesis.
interpretationOur findings provide novel insights into the CMML stem cell compartment, revealing an unexpected degree of heterogeneity and demonstrating that CMML stem cell transcriptomes anticipate disease morphology, and therefore outcome.
fundingProject funding was supported by Oglesby Charitable Trust, Cancer Research UK, Blood Cancer UK, and UK Medical Research Council.
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