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

Author:

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

Abstract

SummaryImpaired 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.

Funder

National Natural Science Foundation

National Natural Science Fund for Distinguished Young Scholar

Innovative Research Group

973 Program

863 Program

National Public Health Grand Research Foundation

Publisher

Georg Thieme Verlag KG

Subject

Hematology

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