Apoptosis in Megakaryocytes: Safeguard and Threat for Thrombopoiesis

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Jan 23

PMID 36685543

Authors

Shuo Yang

Long Wang

Yuesong Wu

Anguo Wu

Feihong Huang

Xiaoqin Tang

Fahsai Kantawong

Songyot Anuchapreeda

Dalian Qin

Qibing Mei

Jianping Chen

Xinwu Huang

Chunxiang Zhang

Jianming Wu

Affiliations

Soon will be listed here.

Abstract

Platelets, generated from precursor megakaryocytes (MKs), are central mediators of hemostasis and thrombosis. The process of thrombopoiesis is extremely complex, regulated by multiple factors, and related to many cellular events including apoptosis. However, the role of apoptosis in thrombopoiesis has been controversial for many years. Some researchers believe that apoptosis is an ally of thrombopoiesis and platelets production is apoptosis-dependent, while others have suggested that apoptosis is dispensable for thrombopoiesis, and is even inhibited during this process. In this review, we will focus on this conflict, discuss the relationship between megakaryocytopoiesis, thrombopoiesis and apoptosis. In addition, we also consider why such a vast number of studies draw opposite conclusions of the role of apoptosis in thrombopoiesis, and try to figure out the truth behind the mystery. This review provides more comprehensive insights into the relationship between megakaryocytopoiesis, thrombopoiesis, and apoptosis and finds some clues for the possible pathological mechanisms of platelet disorders caused by abnormal apoptosis.

Citing Articles

Reactive oxygen species: Orchestrating the delicate dance of platelet life and death.

Liao R, Wang L, Zeng J, Tang X, Huang M, Kantawong F Redox Biol. 2025; 80:103489.

PMID: 39764976 PMC: 11759559. DOI: 10.1016/j.redox.2025.103489.

The lung is a megakaryocyte outpost that can defend against thrombocytopenic attack.

Yeung A, Murphy G J Clin Invest. 2024; 134(22).

PMID: 39545421 PMC: 11563664. DOI: 10.1172/JCI186111.

A modern overview of the process of platelet formation (thrombocytopoiesis) and its dependence on several factors.

Ivanovna Gabrilchak A, Anatolievna Gusyakova O, Aleksandrovich Antipov V, Alekseevna Medvedeva E, Leonidovna Tukshumskaya L Biochem Med (Zagreb). 2024; 34(3):030503.

PMID: 39435166 PMC: 11493462. DOI: 10.11613/BM.2024.030503.

References

Goldfarb A . Megakaryocytic programming by a transcriptional regulatory loop: A circle connecting RUNX1, GATA-1, and P-TEFb. J Cell Biochem. 2009; 107(3):377-82. PMC: 2775554. DOI: 10.1002/jcb.22142. View

Bergmeier W, Burger P, Piffath C, Hoffmeister K, Hartwig J, Nieswandt B . Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro-aged or -injured mouse platelets. Blood. 2003; 102(12):4229-35. DOI: 10.1182/blood-2003-04-1305. View

Rosich L, Colomer D, Roue G . Autophagy controls everolimus (RAD001) activity in mantle cell lymphoma. Autophagy. 2012; 9(1):115-7. PMC: 3542214. DOI: 10.4161/auto.22483. View

Sim X, Jarocha D, Hayes V, Hanby H, Marks M, Camire R . Identifying and enriching platelet-producing human stem cell-derived megakaryocytes using factor V uptake. Blood. 2017; 130(2):192-204. PMC: 5510789. DOI: 10.1182/blood-2017-01-761049. View

Tijssen M, Ghevaert C . Transcription factors in late megakaryopoiesis and related platelet disorders. J Thromb Haemost. 2013; 11(4):593-604. PMC: 3824237. DOI: 10.1111/jth.12131. View

Haas S, Hansson J, Klimmeck D, Loeffler D, Velten L, Uckelmann H . Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors. Cell Stem Cell. 2015; 17(4):422-34. DOI: 10.1016/j.stem.2015.07.007. View

Oltersdorf T, Elmore S, Shoemaker A, Armstrong R, Augeri D, Belli B . An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005; 435(7042):677-81. DOI: 10.1038/nature03579. View

Prasad B, Grimm D, Strauch S, Erzinger G, Corydon T, Lebert M . Influence of Microgravity on Apoptosis in Cells, Tissues, and Other Systems In Vivo and In Vitro. Int J Mol Sci. 2020; 21(24). PMC: 7764784. DOI: 10.3390/ijms21249373. View

Raghuwanshi S, Gutti U, Kandi R, Gutti R . MicroRNA-9 promotes cell proliferation by regulating RUNX1 expression in human megakaryocyte development. Cell Prolif. 2017; 51(1). PMC: 6528850. DOI: 10.1111/cpr.12414. View

10.

Machlus K, Johnson K, Kulenthirarajan R, Forward J, Tippy M, Soussou T . CCL5 derived from platelets increases megakaryocyte proplatelet formation. Blood. 2015; 127(7):921-6. PMC: 4760093. DOI: 10.1182/blood-2015-05-644583. View

11.

Plasilova M, Zivny J, Jelinek J, Neuwirtova R, cermak J, Necas E . TRAIL (Apo2L) suppresses growth of primary human leukemia and myelodysplasia progenitors. Leukemia. 2002; 16(1):67-73. DOI: 10.1038/sj.leu.2402338. View

12.

Wang C, Sample K, Gajendran B, Kapranov P, Liu W, Hu A . FLI1 Induces Megakaryopoiesis Gene Expression Through WAS/WIP-Dependent and Independent Mechanisms; Implications for Wiskott-Aldrich Syndrome. Front Immunol. 2021; 12:607836. PMC: 7953068. DOI: 10.3389/fimmu.2021.607836. View

13.

Sandhya A, Prajapat B . Thrombocytopenia in HIV patients coinfected with tuberculosis. J Family Med Prim Care. 2018; 6(4):859-861. PMC: 5848413. DOI: 10.4103/jfmpc.jfmpc_250_17. View

14.

Huang H, Yu M, Akie T, Moran T, Woo A, Tu N . Differentiation-dependent interactions between RUNX-1 and FLI-1 during megakaryocyte development. Mol Cell Biol. 2009; 29(15):4103-15. PMC: 2715817. DOI: 10.1128/MCB.00090-09. View

15.

Hu J, Li B, Apisa L, Yu H, Entenman S, Xu M . ER stress inhibitor attenuates hearing loss and hair cell death in Cdh23 mutant mice. Cell Death Dis. 2016; 7(11):e2485. PMC: 5260868. DOI: 10.1038/cddis.2016.386. View

16.

Cabrera S, Marino G, Fernandez A, Lopez-Otin C . Autophagy, proteases and the sense of balance. Autophagy. 2010; 6(7):961-3. DOI: 10.4161/auto.6.7.13065. View

17.

Grozovsky R, Giannini S, Falet H, Hoffmeister K . Regulating billions of blood platelets: glycans and beyond. Blood. 2015; 126(16):1877-84. PMC: 4608239. DOI: 10.1182/blood-2015-01-569129. View

18.

Zhang J, Wu K, Xiao X, Liao J, Hu Q, Chen H . Autophagy as a regulatory component of erythropoiesis. Int J Mol Sci. 2015; 16(2):4083-94. PMC: 4346945. DOI: 10.3390/ijms16024083. View

19.

Kraemer B, Hennis I, Karge A, Kraemer A, Dreyer T, Kiechle M . Platelet mitochondrial membrane depolarization reflects disease severity in patients with preeclampsia. Mol Med. 2022; 28(1):51. PMC: 9066965. DOI: 10.1186/s10020-022-00472-x. View

20.

Yang L, Wang L, Zhao C, Zhu X, Hou Y, Jun P . Contributions of TRAIL-mediated megakaryocyte apoptosis to impaired megakaryocyte and platelet production in immune thrombocytopenia. Blood. 2010; 116(20):4307-16. DOI: 10.1182/blood-2010-02-267435. View