Oncotarget

Research Papers:

A TET2 rs3733609 C/T genotype is associated with predisposition to the myeloproliferative neoplasms harboring JAK2V617F and confers a proliferative potential on erythroid lineages

Xiao-hui Shen, Nan-nan Sun, Ya-fei Yin, Su-fang Liu, Xiao-liu Liu, Hong-ling Peng, Chong-wen Dai, Yun-xiao Xu, Ming-yang Deng, Yun-ya Luo, Wen-li Zheng and Guang-sen Zhang _

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Oncotarget. 2016; 7:9550-9560. https://doi.org/10.18632/oncotarget.7072

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Abstract

Xiao-hui Shen1, Nan-nan Sun1, Ya-fei Yin1, Su-fang Liu1, Xiao-liu Liu1, Hong-ling Peng1, Chong-wen Dai1, Yun-xiao Xu1, Ming-yang Deng1, Yun-ya Luo1, Wen-li Zheng1, Guang-sen Zhang1

1Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China

Correspondence to:

Guang-sen Zhang, e-mail: zgsllzy@163.com

Keywords: myeloproliferative neoplasms, TET2, rs3733609, clinical significance, mechanisms

Received: August 19, 2015     Accepted: January 13, 2016     Published: January 29, 2016

ABSTRACT

Common germline single-nucleotide polymorphisms (SNPs) at JAK2 locus have been associated with Myeloproliferative neoplasms (MPN). And, the germline sequence variant rs2736100 C in TERT is related to risk of MPN, suggesting a complex association between SNPs and the pathogenesis of MPN. Our previous study (unpublished data) showed that there was a high frequency distribution in rs3733609 C/T genotype at Ten-Eleven Translocation 2 (TET2) locus in one Chinese familial primary myelofibrosis. In the present study, we evaluate the role and clinical significance of rs3733609 C/T genotype in JAK2V617F-positive sporadic MPN (n = 181). TET2 rs3733609 C/T genotype had a higher incidence (13.81%; 25/181) in JAK2V617F-positive sporadic MPN patients than that in normal controls (n = 236) (6.35%; 15/236), which was predisposing to MPN (odds ratio(OR) = 2.361; P = 0.01). MPN patients with rs3733609 C/T genotype had increased leukocyte and platelets counts, elevated hemoglobin concentration in comparison with T/T genotype. Thrombotic events were more common in MPN patients with rs3733609 C/T than those with T/T genotype (P < 0.01). We confirmed that rs3733609 C/T genotype downregulated TET2 mRNA transcription, and the mechanism may be involved in a disruption of the interaction between CCAAT/enhancer binding protein alpha (C/EBPA) and TET2 rs3733609 C/T locus.TET2 rs3733609 C/T genotype stimulated the erythroid hematopoiesis in MPN patients. Altogether, we found a novel hereditary susceptible factor-TET2 rs3733609 C/T variant for the development of MPN, suggesting the variant may be partially responsible for the pathogenesis and accumulation of MPN.


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