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Thromb Haemost 2015; 113(05): 1021-1034
DOI: 10.1160/TH14-04-0342
Cellular Haemostasis and Platelets
Schattauer GmbH

Low-dose decitabine promotes megakaryocyte maturation and platelet production in healthy controls and immune thrombocytopenia

Hai Zhou
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Yu Hou
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Xuena Liu
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Jihua Qiu
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Qi Feng
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Yawen Wang
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Xu Zhang
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Yanan Min
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Linlin Shao
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Xinguang Liu
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Guosheng Li
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Lizhen Li
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Lei Yang
2   Department of Hematology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
,
Shuqian Xu
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Heyu Ni
3   Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, University of Toronto, Toronto, Canada
,
Jun Peng
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
4   Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China
,
Ming Hou
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
› Institutsangaben Financial support: This work was supported by grants from Tai Shan Scholar Foundation, Clinical Medicine Center Foundation of Shandong Province, Leading Medical Professional Foundation of Shandong Province, National Natural Science Foundation of China (No. 81100334, No. 81100335, No. 81100336, No. 81100348, No. 81170475, No. 81200344, No. 81270578, No. 81300383, No. 81370623, No. 81370616, No. 81300384, No. 81300382), National Natural Science Fund for Distinguished Young Scholar (No. 81125002), State Program of National Natural Science Foundation of China for Innovative Research Group (No. 81321061), 973 Program (No. 2011CB503906), 863 Program (No. 2012AA02A505), State Key Clinical Specialty of China for Blood Disorders, National Public Health Grand Research Foundation (No. 201202017).
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Publikationsverlauf

Received: 11. April 2014

Accepted after major revision: 23. Januar 2014

Publikationsdatum:
24. November 2017 (online)

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Summary

Impaired megakaryocyte maturation and insufficient platelet production have been shown to participate in the pathogenesis of immune thrombocytopenia (ITP). Our previous study demonstrated that low expression of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in megakaryocytes contributed to impaired platelet production in ITP. Decitabine (DAC), a demethylating agent, is known to promote cell differentiation and maturation at low doses. However, whether decitabine is potential in promoting megakaryocyte maturation and platelet release in ITP is unclear. In this study, we evaluated the effect of DAC on megakaryocyte maturation and platelet release in the presence of ITP plasma that has been shown to cause impaired megakaryocyte maturation and platelet production. We observed that low-dose DAC (10 nM) could significantly increase the number of mature polyploid (≥ 4N) megakaryocytes in cultures with plasma from healthy controls and more than one-half of ITP patients in vitro. Furthermore, the number of platelets released from these megakaryocytes significantly increased compared with those untreated with DAC. In these megakaryocytes, DAC significantly enhanced TRAIL expression via decreasing its promoter methylation status. These findings demonstrate that low-dose DAC can promote megakaryocyte maturation and platelet production and enhance TRAIL expression in megakaryocytes in healthy controls and ITP. The potential therapeutic role of low-dose DAC may be beneficial for thrombocytopenic disorders.

H. Z. and Y. H. contributed equally to this work.

Keywords

Immune thrombocytopenia - decitabine - megakaryocyte - platelet - TRAIL
 

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