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The role of apoptosis in megakaryocytes and platelets
Author(s) -
Kile Benjamin T.
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12757
Subject(s) - megakaryocyte , apoptosis , platelet , microbiology and biotechnology , limiting , cancer research , biology , function (biology) , programmed cell death , chemistry , haematopoiesis , immunology , biochemistry , stem cell , mechanical engineering , engineering
Summary 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 BH 3 mimetic drugs that target BCL 2 family proteins to induce apoptosis in tumour cells: agents such as ABT ‐263 (navitoclax, which targets BCL 2, BCL‐X L [BCL2L1] and BCL 2L2) and ABT ‐199 (a BCL 2‐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‐X L . It transpires that the anucleate platelet contains a classical intrinsic apoptosis pathway, which at steady state regulates its life span in the circulation. BCL‐X L 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.