ArticlePathology oncology research : POR2014
The TPO/c-MPL pathway in the bone marrow may protect leukemia cells from chemotherapy in AML Patients.
Article in Pathology oncology research : POR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- The Role of the Bone Marrow Microenvironment in the Pathogenesis of Acute Myeloid Leukemia.Biomedicines · 2026Review
- Development of multivalent CAR T cells as dual immunotherapy and conditioning agents.Molecular therapy. Oncology · 2025Article
- Human Mesenchymal Stem Cell-Derived Exosomes as Engineering Vehicles of Daunorubicin for Targeted c-Mpl+ AML Therapy.International journal of nanomedicine · 2025Article
- Influence on therapeutic outcome of platelet count at diagnosis in patients with de novo non-APL acute myeloid leukemia.BMC cancer · 2023Article
- Review
- Review
- Dynamic trajectory of platelet counts after the first cycle of induction chemotherapy in AML patients.BMC cancer · 2022Article
- Thrombopoietin-based CAR-T cells demonstrate in vitro and in vivo cytotoxicity to MPL positive acute myelogenous leukemia and hematopoietic stem cells.Gene therapy · 2022Article
- A Role for the Bone Marrow Microenvironment in Drug Resistance of Acute Myeloid Leukemia.Cells · 2021Review
- Overcoming adaptive therapy resistance in AML by targeting immune response pathways.Science translational medicine · 2019Article
- CD110 promotes pancreatic cancer progression and its expression is correlated with poor prognosis.Journal of cancer research and clinical oncology · 2019Article
- c-MPL provides tumor-targeted T-cell receptor-transgenic T cells with costimulation and cytokine signals.Blood · 2017Article
- Multiregion whole-exome sequencing of matched primary and metastatic tumors revealed genomic heterogeneity and suggested polyclonal seeding in colorectal cancer metastasis.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Article
- Cancer stem cell marker glycosylation: Nature, function and significance.Glycoconjugate journal · 2017Review
- H2S protects against fatal myelosuppression by promoting the generation of megakaryocytes/platelets.Journal of hematology & oncology · 2016Article
- Inhibition of poly(ADP-ribose) polymerase 1 protects against acute myeloid leukemia by suppressing the myeloproliferative leukemia virus oncogene.Oncotarget · 2015Article
- Article
- Osteoblasts protect AML cells from SDF-1-induced apoptosis.Journal of cellular biochemistry · 2014Article
- Platelets and cancer: a casual or causal relationship: revisited.Cancer metastasis reviews · 2014Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence indicates that the interaction of human LSCs (leukemic stem cells) with the hematopoietic microenvironment, mediated by the thrombopoietin (TPO)/c-MPL pathway, may be an underlying mechanism for resistance to cell cycle-dependent cytotoxic chemotherapy. However, the role of TPO/c-MPL signaling in AML (acute myelogenous leukemia) chemotherapy resistance hasn't been fully understood. The c-MPL and TPO levels in different AML samples were measured by flow cytometry and ELISA. We also assessed the TPO levels in the osteoblasts derived from bone mesenchymal stem cells (BMSCs). The survival rate of an AML cell line that had been co-cultured with different BMSC-derived osteoblasts was measured to determine the IC50 of an AML chemotherapy drug daunorubicin (DNR). The levels of TPO/c-MPL in the initial and relapse AML patients were significantly higher than that in the control (P < 0.05). The osteoblasts derived from AML patients' BMSCs secreted more TPO than the osteoblasts derived from normal control BMSCs (P < 0.05). A strong positive correlation between the TPO level and c-MPL expression was found in the bone marrow mononuclear cells of the relapse AML patients. More importantly, the IC50 of DNR in the HEL + AML-derived osteoblasts was the highest among all co-culture systems. High level of TPO/c-MPL signaling may protect LSCs from chemotherapy in AML. The effects of inhibition of the TPO/c-MPL pathway on enhancing the chemotherapy sensitivity of AML cells, and on their downstream effector molecules that direct the interactions between patient-derived blasts and leukemia repopulating cells need to be further studied.
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