ArticleBlood2012
Thrombopoietin/MPL participates in initiating and maintaining RUNX1-ETO acute myeloid leukemia via PI3K/AKT signaling.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- Recombinant human thrombopoietin promotes platelet engraftment after umbilical cord blood transplantation.Blood advances · 2020Trial
- IBI-DT: a novel approach combining individualized Bayesian inference and decision tree for identifying cancer drivers and their interactions.Briefings in bioinformatics · 2025Article
- Human Mesenchymal Stem Cell-Derived Exosomes as Engineering Vehicles of Daunorubicin for Targeted c-Mpl+ AML Therapy.International journal of nanomedicine · 2025Article
- PHF6 suppresses self-renewal of leukemic stem cells in AML.bioRxiv : the preprint server for biology · 2024Article
- c-Mpl-del, a c-Mpl alternative splicing isoform, promotes AMKL progression and chemoresistance.Cell death & disease · 2022Article
- Establishment of a novel mesenchymal stem cell-based regimen for chronic myeloid leukemia differentiation therapy.Cell death & disease · 2021Article
- Review
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- Systematic discovery of the functional impact of somatic genome alterations in individual tumors through tumor-specific causal inference.PLoS computational biology · 2019Article
- Romiplostim-related myelofibrosis in refractory primary immune thrombocytopenia: A Case report.Medicine · 2019Article
- Different roles of E proteins in t(8;21) leukemia: E2-2 compromises the function of AETFC and negatively regulates leukemogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A network map of thrombopoietin signaling.Journal of cell communication and signaling · 2018Article
- Domain retention in transcription factor fusion genes and its biological and clinical implications: a pan-cancer study.Oncotarget · 2017Article
- Article
- Role of RUNX1 in hematological malignancies.Blood · 2017Review
- Update on acute myeloid leukemia stem cells: New discoveries and therapeutic opportunities.World journal of stem cells · 2016Review
- Immortalization of human AE pre-leukemia cells by hTERT allows leukemic transformation.Oncotarget · 2016Article
- UBASH3B/Sts-1-CBL axis regulates myeloid proliferation in human preleukemia induced by AML1-ETO.Leukemia · 2016Article
- Heterogeneity of leukemia-initiating capacity of chronic myelogenous leukemia stem cells.The Journal of clinical investigation · 2016Article
- Overexpression of ATP1B1 predicts an adverse prognosis in cytogenetically normal acute myeloid leukemia.Oncotarget · 2016Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Oncogenic mutations in components of cytokine signaling pathways elicit ligand-independent activation of downstream signaling, enhancing proliferation and survival in acute myeloid leukemia (AML). The myeloproliferative leukemia virus oncogene, MPL, a homodimeric receptor activated by thrombopoietin (THPO), is mutated in myeloproliferative disorders but rarely in AML. Here we show that wild-type MPL expression is increased in a fraction of human AML samples expressing RUNX1-ETO, a fusion protein created by chromosome translocation t(8;21), and that up-regulation of Mpl expression in mice induces AML when coexpressed with RUNX1-ETO. The leukemic cells are sensitive to THPO, activating survival and proliferative responses. Mpl expression is not regulated by RUNX1-ETO in mouse hematopoietic progenitors or leukemic cells. Moreover, we find that activation of PI3K/AKT but not ERK/MEK pathway is a critical mediator of the MPL-directed antiapoptotic function in leukemic cells. Hence, this study provides evidence that up-regulation of wild-type MPL levels promotes leukemia development and maintenance through activation of the PI3K/AKT axis, and suggests that inhibitors of this axis could be effective for treatment of MPL-positive AML.
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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.