Methylated alteration of SHP1 complements mutation of JAK2 tyrosine kinase in patients with myeloproliferative neoplasm

doi:10.7314/apjcp.2015.16.6.2219

科研成果详情

题名	Methylated alteration of SHP1 complements mutation of JAK2 tyrosine kinase in patients with myeloproliferative neoplasm
作者	Yang, Jun-Jun1; Chen, Hui1; Zheng, Xiao-Qun1; Li, Hai-Ying 2; Wu, Jian-Bo2; Tang, Li-Yuan3; Gao, Shen-Meng2
发表日期	2015
发表期刊	Asian Pacific journal of cancer prevention : APJCP 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Hypermethylation Myeloproliferative neoplasm patients SHP1
摘要	SHP1 negatively regulates the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Promoter hypermethylation resulting in epigenetic inactivation of SHP1 has been reported in myelomas, leukemias and other cancers. However, whether SHP1 hypermethylation occurs in MPNs, especially in Chinese patients, has remained unclear. Here, we report that aberrant hypermethylation of SHP1 was observed in several leukemic cell lines and bone marrow mononuclear cells from MPN patients. About 51 of 118 (43.2%) MPN patients including 23 of 50 (46%) polycythaemia vera patients, 20 of 50 (40%) essential thrombocythaemia and 8 of 18 (44.4%) idiopathic myelofibrosis showed hypermethylation by methylation-specific polymerase chain reaction. However, SHP1 methylation was not measured in 20 healthy volunteers. Hypermethylation of SHP1 was found in MPN patients with both positive (34/81, 42%) and negative (17/37, 45.9%) JAK2V617F mutation. The levels of SHP1 mRNA were significantly lower in hypermethylated samples than unmethylated samples, suggesting SHP1 may be epigenetically inactivated in MPN patients. Furthermore, treatment with 5-aza-2'-deoxycytidine (AZA) in K562 cells showing hypermethylation of SHP1 led to progressive demethylation of SHP1, with consequently increased reexpression of SHP1. Meanwhile, phosphorylated JAK2 and STAT3 were progressively reduced. Finally, AZA increased the expression of SHP1 in primary MPN cells with hypermethylation of SHP1. Therefore, our data suggest that epigenetic inactivation of SHP1 contributes to the constitutive activation of JAK2/STAT signaling. Restoration of SHP1 expression by AZA may contribute to clinical treatment for MPN patients.
出版者	Asian Pacific Organization for Cancer Preventionkyyoo@plaza.snu.ac.kr
ISSN	1513-7368
卷号	16 期号:6 页码:2219-25.
DOI	10.7314/apjcp.2015.16.6.2219
收录类别	PUBMED ; SCOPUS
URL	查看原文
PubMed ID	25824741
SCOPUSEID	2-s2.0-84929207628
通讯作者地址	[Gao, Shen-Meng]Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Epidemiology;Oncology;Public Health, Environmental and Occupational Health;Cancer Research
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/34818
专题	第二临床医学院，附属第二医院、育英儿童医院附属第一医院附属第一医院_内科实验室
通讯作者	Gao, Shen-Meng
作者单位	1.Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China; 2.Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 3.Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院
通讯作者单位	附属第一医院_内科实验室
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Yang, Jun-Jun,Chen, Hui,Zheng, Xiao-Qun,et al. Methylated alteration of SHP1 complements mutation of JAK2 tyrosine kinase in patients with myeloproliferative neoplasm[J]. Asian Pacific journal of cancer prevention : APJCP,2015,16(6):2219-25..
APA	Yang, Jun-Jun., Chen, Hui., Zheng, Xiao-Qun., Li, Hai-Ying., Wu, Jian-Bo., ... & Gao, Shen-Meng. (2015). Methylated alteration of SHP1 complements mutation of JAK2 tyrosine kinase in patients with myeloproliferative neoplasm. Asian Pacific journal of cancer prevention : APJCP, 16(6), 2219-25..
MLA	Yang, Jun-Jun,et al."Methylated alteration of SHP1 complements mutation of JAK2 tyrosine kinase in patients with myeloproliferative neoplasm".Asian Pacific journal of cancer prevention : APJCP 16.6(2015):2219-25..