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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2019

Open Access 01-12-2019 | Acute Myeloid Leukemia | Research

Genetic polymorphisms of histone methyltransferase SETD2 predicts prognosis and chemotherapy response in Chinese acute myeloid leukemia patients

Authors: Suwei Wang, Xiaoqing Yuan, Yazhen Liu, Kewei Zhu, Peng Chen, Han Yan, Daoyu Zhang, Xi Li, Hui Zeng, Xielan Zhao, Xiaoping Chen, Gan Zhou, Shan Cao

Published in: Journal of Translational Medicine | Issue 1/2019

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Abstract

Background

SETD2, the single mediator of trimethylation of histone 3 at position lysine 36, has been reported associated with initiation progression and chemotherapy resistance in acute myeloid leukemia (AML). Whether polymorphisms of SETD2 affect prognosis and chemotherapy response of AML remains elusive.

Methods

Three tag single-nucleotide polymorphisms (tagSNPs) of SETD2 were genotyped in 579 AML patients by using Sequenom Massarray system. Association of the SNPs with complete remission (CR) rate after Ara-C based induction therapy, overall survival (OS) and relapse-free survival (RFS) were analyzed.

Result

Survival analysis indicated that SETD2 rs76208147 TT genotype was significantly associated with poor prognosis of AML (TT vs. CC + CT hazard ratio: HR = 1.838, 95% confidence interval (CI) 1.005–3.360, p = 0.048). After adjusting for the known prognostic factors including risk stratification, age, allo-SCT, WBC count and LDH count, rs76208147 TT genotype was still associated with OS in the multivariate analysis (TT vs. CC + CT HR = 1.923, 95% CI 1.007–3.675, p = 0.048). In addition, after adjusting by other clinical features, patients with rs4082155  allele G carries showed higher rate of complete remission which indicated by CR rate (AG + GG vs. AA odd ratio (OR) = 0.544, 95% CI 0.338–0.876, p = 0.012).

Conclusions

SETD2 genetic polymorphism is associated with AML prognosis and chemotherapy outcome, suggesting the possibility for development in AML diagnostics and therapeutics towards SETD2.
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Metadata
Title
Genetic polymorphisms of histone methyltransferase SETD2 predicts prognosis and chemotherapy response in Chinese acute myeloid leukemia patients
Authors
Suwei Wang
Xiaoqing Yuan
Yazhen Liu
Kewei Zhu
Peng Chen
Han Yan
Daoyu Zhang
Xi Li
Hui Zeng
Xielan Zhao
Xiaoping Chen
Gan Zhou
Shan Cao
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2019
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-019-1848-9

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