ArticleBlood2012
The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
28 citing papers in PubMed, 49 citations in OpenAlex.
- Venetoclax Combined With FLAG-IDA Induction and Consolidation in Newly Diagnosed and Relapsed or Refractory Acute Myeloid Leukemia.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Recombinant human thrombopoietin promotes platelet engraftment after umbilical cord blood transplantation.Blood advances · 2020Trial
- Efficacy of venetoclax combined with hypomethylating agents in young, and unfit patients with newly diagnosed core binding factor acute myeloid leukemia.Blood cancer journal · 2023Article
- Deregulated Gene Expression Profiles and Regulatory Networks in Adult and Pediatric RUNX1/RUNX1T1-Positive AML Patients.Cancers · 2023Article
- Progress in construction of mouse models to investigate the pathogenesis and immune therapy of human hematological malignancy.Frontiers in immunology · 2023Review
- Review
- Article
- An update on the molecular pathogenesis and potential therapeutic targeting of AML with t(8;21)(q22;q22.1);RUNX1-RUNX1T1.Blood advances · 2020Review
- 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
- Nfix Promotes Survival of Immature Hematopoietic Cells via Regulation of c-Mpl.Stem cells (Dayton, Ohio) · 2018Article
- Cancer Stem Cells: Emergent Nature of Tumor Emergency.Frontiers in genetics · 2018Article
- Article
- Protease-activated receptor-1 inhibits proliferation but enhances leukemia stem cell activity in acute myeloid leukemia.Oncogene · 2017Article
- 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
- New insights into transcriptional and leukemogenic mechanisms of AML1-ETO and E2A fusion proteins.Frontiers in biology · 2016Article
- Heterogeneity of leukemia-initiating capacity of chronic myelogenous leukemia stem cells.The Journal of clinical investigation · 2016Article
- UBASH3B/Sts-1-CBL axis regulates myeloid proliferation in human preleukemia induced by AML1-ETO.Leukemia · 2016Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
AML1-ETO (AE) is a fusion product of translocation (8;21) that accounts for 40% of M2 type acute myeloid leukemia (AML). In addition to its role in promoting preleukemic hematopoietic cell self-renewal, AE represses DNA repair genes, which leads to DNA damage and increased mutation frequency. Although this latter function may promote leukemogenesis, concurrent p53 activation also leads to an increased baseline apoptotic rate. It is unclear how AE expression is able to counterbalance this intrinsic apoptotic conditioning by p53 to promote survival and self-renewal. In this report, we show that Bcl-xL is up-regulated in AE cells and plays an essential role in their survival and self-renewal. Further investigation revealed that Bcl-xL expression is regulated by thrombopoietin (THPO)/MPL-signaling induced by AE expression. THPO/MPL-signaling also controls cell cycle reentry and mediates AE-induced self-renewal. Analysis of primary AML patient samples revealed a correlation between MPL and Bcl-xL expression specifically in t(8;21) blasts. Taken together, we propose that survival signaling through Bcl-xL is a critical and intrinsic component of a broader self-renewal signaling pathway downstream of AML1-ETO-induced MPL.
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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.