The role of apoptosis in megakaryocytes and platelets

Kile, Benjamin T.

doi:10.1111/bjh.12757

Cited by 122Platelet Disorders and TreatmentsCell death mechanisms and regulationBlood Coagulation and Thrombosis Mechanisms

The role of apoptosis in megakaryocytes and platelets

Kile, Benjamin T.·2014·British Journal of Haematology

DOI 10.1111/bjh.12757

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Abstract

The role of apoptotic pathways in the development and function of the megakaryocyte lineage has generated renewed interest in recent years. This has been driven by the advent of BH3 mimetic drugs that target BCL2 family proteins to induce apoptosis in tumour cells: agents such as ABT-263 (navitoclax, which targets BCL2, BCL-XL [BCL2L1] and BCL2L2) and ABT-199 (a BCL2-specific agent) are showing great promise in early stage clinical trials. However, the major dose-limiting toxicity of navitoclax has proven to be thrombocytopenia, an on-target effect of inhibiting BCL-XL . It transpires that the anucleate platelet contains a classical intrinsic apoptosis pathway, which at steady state regulates its life span in the circulation. BCL-XL is the critical pro-survival protein that restrains apoptosis and maintains platelet viability. These findings have paved the way to a deeper understanding of apoptotic pathways and processes in platelets, and their precursor cell, the megakaryocyte.

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Programmed cell death (PCD) pathways, including apoptosis and regulated necrosis, are required for normal cell turnover and tissue homeostasis.
“Programmed cell death (PCD) pathways, including apoptosis and regulated necrosis, are required for normal cell turnover and tissue homeostasis.”
From Programmed cell death in aging (2015) · cites this paper as Kile, 2014
In the adult, PCD is required for the normal turnover of cells in numerous tissues that are maintained by cell division, including the intestinal epithelium, the blood, the epidermis, kidney and lungs.
“In the adult, PCD is required for the normal turnover of cells in numerous tissues that are maintained by cell division, including the intestinal epithelium, the blood, the epidermis, kidney and lungs(Elmore, 2007; Gunther et al., 2013; Kile, 2014).”
From Programmed cell death in aging (2015) · cites this paper as Kile, 2014

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Authors: Kile, B. T.
Affiliations: The University of Melbourne (AU)
Corresponding author: Kile, Benjamin T.
ORCID: Kile, Benjamin T.
Venue: British Journal of Haematology
Publisher: Wiley
Published: 2014-01-28
Volume: 165
Issue: 2
Pages: 217-226
ISSN: 0007-1048 (ISSN-L)
1365-2141
DOI: 10.1111/bjh.12757
OpenAlex: W2039004541
Cited by: 122
References: 96
Citations by year: 2026: 3 · 2025: 1 · 2024: 8 · 2023: 9 · 2022: 10 · 2021: 12 · 2020: 12 · 2019: 11 · 2018: 10 · 2017: 11 · 2016: 19 · 2015: 14 · 2014: 2
FWCI: 2.34
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: British Journal of Haematology (publishedVersion)
PubMed (publishedVersion)
Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Topics: Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords: apoptosis, megakaryocytes, platelets, Bcl-xL, Bcl-2 family proteins, BH3 mimetics, navitoclax, venetoclax, thrombocytopenia, platelet survival, megakaryopoiesis
MeSH terms: Animals, Blood Platelets, Humans, Megakaryocytes, Signal Transduction, Platelet Activation, Apoptosis, Caspases

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The role of apoptosis in megakaryocytes and platelets

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