ArticleThe Journal of experimental medicine2011
Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets.
Article in The Journal of experimental medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 184 citations in OpenAlex.
- Chemotherapy-induced thrombocytopenia: from "platelet counting" to ecological repair of the bone marrow.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Review
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- Converging Molecular Mechanisms of Nucleated Cell Death Pathways and Procoagulant Platelet Formation.Cells · 2025Review
- Histone lysine methyltransferases MLL3 and MLL4 direct gene expression to produce platelets efficiently.Nature communications · 2025Article
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- Platelets and mitochondria: the calcium connection.Molecular biology reports · 2025Review
- A bacterial effector manipulates host lysosomal protease activity-dependent plasticity in cell death modalities to facilitate infection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Comparative small molecule screening of primary human acute leukemias, engineered human leukemia and leukemia cell lines.Leukemia · 2025Article
- AMPK inhibition sensitizes acute leukemia cells to BH3 mimetic-induced cell death.Cell death and differentiation · 2024Article
- CBFA2T3::GLIS2 pediatric acute megakaryoblastic leukemia is sensitive to BCL-XL inhibition by navitoclax and DT2216.Blood advances · 2024Article
- Immune attack on megakaryocytes in immune thrombocytopenia.Research and practice in thrombosis and haemostasis · 2024Article
- Chlorogenic acid compounds from sweetpotato (Frontiers in pharmacology · 2024Article
- Integrative analysis reveals novel insights into juvenile idiopathic arthritis pathogenesis and shared molecular pathways with associated traits.Frontiers in genetics · 2024Article
- Role of Nitric Oxide in Megakaryocyte Function.International journal of molecular sciences · 2023Review
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Treatment of chemotherapy-induced thrombocytopenia in patients with non-hematologic malignancies.Haematologica · 2022Article
- What can we learn from mice lacking pro-survival BCL-2 proteins to advance BH3 mimetic drugs for cancer therapy?Cell death and differentiation · 2022Review
- Interferon α-induced SAMHD1 regulates human cultured megakaryocyte apoptosis and proplatelet formation.Haematologica · 2022Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is believed that megakaryocytes undergo a specialized form of apoptosis to shed platelets. Conversely, a range of pathophysiological insults, including chemotherapy, are thought to cause thrombocytopenia by inducing the apoptotic death of megakaryocytes and their progenitors. To resolve this paradox, we generated mice with hematopoietic- or megakaryocyte-specific deletions of the essential mediators of apoptosis, Bak and Bax. We found that platelet production was unperturbed. In stark contrast, deletion of the prosurvival protein Bcl-x(L) resulted in megakaryocyte apoptosis and a failure of platelet shedding. This could be rescued by deletion of Bak and Bax. We examined the effect on megakaryocytes of three agents that activate the intrinsic apoptosis pathway in other cell types: etoposide, staurosporine, and the BH3 mimetic ABT-737. All three triggered mitochondrial damage, caspase activation, and cell death. Deletion of Bak and Bax rendered megakaryocytes resistant to etoposide and ABT-737. In vivo, mice with a Bak(-/-) Bax(-/-) hematopoietic system were protected against thrombocytopenia induced by the chemotherapeutic agent carboplatin. Thus, megakaryocytes do not activate the intrinsic pathway to generate platelets; rather, the opposite is true: they must restrain it to survive and progress safely through proplatelet formation and platelet shedding.
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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.