title: Low-dose decitabine promotes megakaryocyte maturation and platelet production in healthy controls and immune thrombocytopenia.
abstract: 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.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhou
authors.forename: Yu
authors.initials: Y
authors.lastname: Hou
authors.forename: Xuena
authors.initials: X
authors.lastname: Liu
authors.forename: Jihua
authors.initials: J
authors.lastname: Qiu
authors.forename: Qi
authors.initials: Q
authors.lastname: Feng
authors.forename: Yawen
authors.initials: Y
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Yanan
authors.initials: Y
authors.lastname: Min
authors.forename: Linlin
authors.initials: L
authors.lastname: Shao
authors.forename: Xinguang
authors.initials: X
authors.lastname: Liu
authors.forename: Guosheng
authors.initials: G
authors.lastname: Li
authors.forename: Lizhen
authors.initials: L
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Shuqian
authors.initials: S
authors.lastname: Xu
authors.forename: Heyu
authors.initials: H
authors.lastname: Ni
authors.affiliation: Jun Peng, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong, 250012, China, Tel.: +86 531 82169867, Fax: +86 531 86927544, E-mail: junpeng88@sina.com.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.affiliation: Ming Hou, Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong, 250012, China, Tel.: +86 531 82169879, Fax: +86 531 86927544, E-mail: houming@medmail.com.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Hou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001483:Base Sequence; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D018899:CpG Islands; D019175:DNA Methylation; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects*; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood* / Q000188:drug therapy*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood; D013921:Thrombocytopenia; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D000077209:Decitabine; D001374:Azacitidine
keywords: Immune thrombocytopenia; TRAIL; decitabine; megakaryocyte; platelet