ArticleThe Journal of clinical investigation2016
Heterogeneity of leukemia-initiating capacity of chronic myelogenous leukemia stem cells.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Imbalance of c-MPL Isoform Promotes Tumorigenesis by Activating STAT-5 in Leukemic Cell Lines.Current issues in molecular biology · 2026Article
- CD73: a new immune checkpoint for leukemia treatment.Frontiers in immunology · 2025Review
- Novel targeted therapies in chronic myeloid leukemia.Pharmaceutical science advances · 2024Review
- Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia: Strategies to Optimize Success and New Directions.Current hematologic malignancy reports · 2024Review
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- The dark side of stemness - the role of hematopoietic stem cells in development of blood malignancies.Frontiers in oncology · 2024Review
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- Ex Vivo Expansion of Phenotypic and Transcriptomic Chronic Myeloid Leukemia Stem Cells.Experimental hematology · 2022Article
- Non-Coding RNAs Are Implicit in Chronic Myeloid Leukemia Therapy Resistance.International journal of molecular sciences · 2022Review
- Isolation, Maintenance and Expansion of Adult Hematopoietic Stem/Progenitor Cells and Leukemic Stem Cells.Cancers · 2022Review
- Leukemia Stem Cell Frequency at Diagnosis Correlates With Measurable/Minimal Residual Disease and Impacts Survival in Adult Acute Myeloid Leukemia.Frontiers in oncology · 2022Article
- Integrated Analysis of miRNA-mRNA Expression in Mink Lung Epithelial Cells Infected With Canine Distemper Virus.Frontiers in veterinary science · 2022Article
- MicroRNA-18a-5p regulates the Warburg effect by targeting hypoxia-inducible factor 1α in the K562/ADM cell line.Experimental and therapeutic medicine · 2021Article
- Leukaemia: a model metastatic disease.Nature reviews. Cancer · 2021Review
- Targeting Leukemic Stem Cells in Chronic Myeloid Leukemia: Is It Worth the Effort?International journal of molecular sciences · 2021Review
- Establishment of a novel mesenchymal stem cell-based regimen for chronic myeloid leukemia differentiation therapy.Cell death & disease · 2021Article
- Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms.International journal of molecular sciences · 2021Review
- Combined GSTT1 Null, GSTM1 Null and XPD Lys/Lys Genetic Polymorphisms and Their Association with Increased Risk of Chronic Myeloid Leukemia.Pharmacogenomics and personalized medicine · 2021Article
- The quiescent fraction of chronic myeloid leukemic stem cells depends on BMPR1B, Stat3 and BMP4-niche signals to persist in patients in remission.Haematologica · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic myelogenous leukemia (CML) results from transformation of a long-term hematopoietic stem cell (LTHSC) by expression of the BCR-ABL fusion gene. However, BCR-ABL-expressing LTHSCs are heterogeneous in their capacity as leukemic stem cells (LSCs). Although discrepancies in proliferative, self-renewal, and differentiation properties of normal LTHSCs are being increasingly recognized, the mechanisms underlying heterogeneity of leukemic LTHSCs are poorly understood. Using a CML mouse model, we identified gene expression differences between leukemic and nonleukemic LTHSCs. Expression of the thrombopoietin (THPO) receptor MPL was elevated in leukemic LTHSC populations. Compared with LTHSCs with low MPL expression, LTHSCs with high MPL expression showed enhanced JAK/STAT signaling and proliferation in response to THPO in vitro and increased leukemogenic capacity in vivo. Although both G0 and S phase subpopulations were increased in LTHSCs with high MPL expression, LSC capacity was restricted to quiescent cells. Inhibition of MPL expression in CML LTHSCs reduced THPO-induced JAK/STAT signaling and leukemogenic potential. These same phenotypes were also present in LTHSCs from patients with CML, and patient LTHSCs with high MPL expression had reduced sensitivity to BCR-ABL tyrosine kinase inhibitor treatment but increased sensitivity to JAK inhibitors. Together, our studies identify MPL expression levels as a key determinant of heterogeneous leukemia-initiating capacity and drug sensitivity of CML LTHSCs and suggest that high MPL-expressing CML stem cells are potential targets for therapy.
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