ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Identification of CD25 as STAT5-Dependent Growth Regulator of Leukemic Stem Cells in Ph+ CML.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Role of CD25 expression on prognosis of acute myeloid leukemia: A literature review and meta-analysis.PloS one · 2020Pooled it
- CD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2017Trial
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- CAR-macrophages targets CD26 to eliminate chronic myeloid leukemia stem cells.Experimental hematology & oncology · 2025Article
- Novel targeted therapies in chronic myeloid leukemia.Pharmaceutical science advances · 2024Review
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- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Unraveling the genetic basis of the causal association between inflammatory cytokines and osteonecrosis.Frontiers in endocrinology · 2024Article
- Hub genes and their key effects on prognosis of Burkitt lymphoma.World journal of clinical oncology · 2023Article
- Genetic separation of chronic myeloid leukemia stem cells from normal hematopoietic stem cells at single-cell resolution.Leukemia · 2023Article
- Upregulation of Tim-3 is associated with poor prognosis in acute myeloid leukemia.Cancer medicine · 2023Article
- Article
- Chimeric antigen-receptor (CAR) engineered natural killer cells in a chronic myeloid leukemia (CML) blast crisis model.Frontiers in immunology · 2023Article
- IL-7 induces type 2 cytokine response in lung ILC2s and regulates GATA3 and CD25 expression.Journal of leukocyte biology · 2022Article
- Isolation, Maintenance and Expansion of Adult Hematopoietic Stem/Progenitor Cells and Leukemic Stem Cells.Cancers · 2022Review
- Leukemic Stem Cell: A Mini-Review on Clinical Perspectives.Frontiers in oncology · 2022Review
- Shedding Light on Targeting Chronic Myeloid Leukemia Stem Cells.Journal of clinical medicine · 2021Review
- Leukemia Stem Cells as a Potential Target to Achieve Therapy-Free Remission in Chronic Myeloid Leukemia.Cancers · 2021Review
- Phenotypic characterization of leukemia-initiating stem cells in chronic myelomonocytic leukemia.Leukemia · 2021Article
- Targeting Leukemic Stem Cells in Chronic Myeloid Leukemia: Is It Worth the Effort?International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeIn chronic myelogenous leukemia (CML), leukemic stem cells (LSC) represent a critical target of therapy. However, little is known about markers and targets expressed by LSCs. The aim of this project was to identify novel relevant markers of CML LSCs. EXPERIMENTAL
designCML LSCs were examined by flow cytometry, qPCR, and various bioassays. In addition, we examined the multipotent CD25(+)CML cell line KU812.
resultsIn contrast to normal hematopoietic stem cells, CD34(+)/CD38(-)CML LSCs expressed the IL-2 receptor alpha chain, IL-2RA (CD25). STAT5 was found to induce expression of CD25 in Lin(-)/Sca-1(+)/Kit(+)stem cells in C57Bl/6 mice. Correspondingly, shRNA-induced STAT5 depletion resulted in decreased CD25 expression in KU812 cells. Moreover, the BCR/ABL1 inhibitors nilotinib and ponatinib were found to decrease STAT5 activity and CD25 expression in KU812 cells and primary CML LSCs. A CD25-targeting shRNA was found to augment proliferation of KU812 cellsin vitroand their engraftmentin vivoin NOD/SCID-IL-2Rγ(-/-)mice. In drug-screening experiments, the PI3K/mTOR blocker BEZ235 promoted the expression of STAT5 and CD25 in CML cells. Finally, we found that BEZ235 produces synergistic antineoplastic effects on CML cells when applied in combination with nilotinib or ponatinib.
conclusionsCD25 is a novel STAT5-dependent marker of CML LSCs and may be useful for LSC detection and LSC isolation in clinical practice and basic science. Moreover, CD25 serves as a growth regulator of CML LSCs, which may have biologic and clinical implications and may pave the way for the development of new more effective LSC-eradicating treatment strategies in CML.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.