ArticleNature communications2015
Dipeptide species regulate p38MAPK-Smad3 signalling to maintain chronic myelogenous leukaemia stem cells.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 63 citations in OpenAlex.
- Super-Enhancer-Driven SOX4/SMAD3 Mediate Membrane Remodeling by Regulating Phospholipid Metabolism to Accelerate Leukemia Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- FBXO3-mediated DUSP9 ubiquitination promotes leukemia stem cell maintenance and tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Cell reports. Medicine · 2026Article
- Arginine Transporters in Human Cancers: Emerging Mechanisms and Clinical Implications.Biomolecules · 2026Review
- Mapping protein-metabolite interactions iniScience · 2025Article
- Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Genes & diseases · 2024Review
- Mutation and cell state compatibility is required and targetable in Ph+ acute lymphoblastic leukemia minimal residual disease.bioRxiv : the preprint server for biology · 2024Article
- Peptide Transporter 1-Mediated Dipeptide Transport Promotes Hepatocellular Carcinoma Metastasis by Activating MAP4K4/G3BP2 Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Metabolic Analysis of DFO-Resistant Huh7 Cells and Identification of Targets for Combination Therapy.Metabolites · 2023Article
- Metabolomics and lipidomics strategies in modern drug discovery and development.Drug discovery today · 2023Review
- Protein-Metabolite Interactions Shape Cellular Metabolism and Physiology.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Rewiring of the protein-protein-metabolite interactome during the diauxic shift in yeast.Cellular and molecular life sciences : CMLS · 2022Article
- Systematic screening and structural characterization of dipeptides using offline 2D LC-LTQ-Orbitrap MS: A case study ofJournal of pharmaceutical analysis · 2022Article
- The miR-200c/141-ZEB2-TGFβ axis is aberrant in human T-cell prolymphocytic leukemia.Haematologica · 2022Article
- Chronic myeloid leukemia stem cells: targeting therapeutic implications.Stem cell research & therapy · 2021Review
- Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1.Molecular medicine (Cambridge, Mass.) · 2021Article
- Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia-From Molecular Mechanisms to Clinical Relevance.Cancers · 2021Review
- Metabolic rewiring is associated with HPV-specific profiles in cervical cancer cell lines.Scientific reports · 2021Article
- New routes to eradicating chronic myelogenous leukemia stem cells by targeting metabolism.International journal of hematology · 2021Review
- Multi-omics analysis of early leaf development inPatterns (New York, N.Y.) · 2021Article
- Global mapping of protein-metabolite interactions in Saccharomyces cerevisiae reveals that Ser-Leu dipeptide regulates phosphoglycerate kinase activity.Communications biology · 2021Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the specific survival of the rare chronic myelogenous leukaemia (CML) stem cell population could provide a target for therapeutics aimed at eradicating these cells. However, little is known about how survival signalling is regulated in CML stem cells. In this study, we survey global metabolic differences between murine normal haematopoietic stem cells (HSCs) and CML stem cells using metabolomics techniques. Strikingly, we show that CML stem cells accumulate significantly higher levels of certain dipeptide species than normal HSCs. Once internalized, these dipeptide species activate amino-acid signalling via a pathway involving p38MAPK and the stemness transcription factor Smad3, which promotes CML stem cell maintenance. Importantly, pharmacological inhibition of dipeptide uptake inhibits CML stem cell activity in vivo. Our results demonstrate that dipeptide species support CML stem cell maintenance by activating p38MAPK-Smad3 signalling in vivo, and thus point towards a potential therapeutic target for CML treatment.
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