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

Hai Zhou; Yu Hou; Xuena Liu; Jihua Qiu; Qi Feng; Yawen Wang; Xu Zhang; Yanan Min; Linlin Shao; Xinguang Liu; Guosheng Li; Lizhen Li; Lei Yang; Shuqian Xu; Heyu Ni; Jun Peng; Ming Hou

doi:10.1160/TH14-04-0342

Thrombosis and Haemostasis, Table of Contents

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

Authors

Hai Zhou

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
Yu Hou

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
Xuena Liu

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
Jihua Qiu

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
Qi Feng

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
Yawen Wang

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
Xu Zhang

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
Yanan Min

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
Linlin Shao

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
Xinguang Liu

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
Guosheng Li

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
Lizhen Li

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
Lei Yang

²Department of Hematology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
Shuqian Xu

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
Heyu Ni

³Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, University of Toronto, Toronto, Canada
Jun Peng

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China

⁴Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China
Ming Hou

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, China

Abstract

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

Full Text

References

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