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Leukemia & Lymphoma Volume 58, 2017 - Issue 8
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Original Articles: Research

Long non-coding RNA GAS5 polymorphism predicts a poor prognosis of acute myeloid leukemia in Chinese patients via affecting hematopoietic reconstitution

Han YanDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, PR China; ;Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, PR China;
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Dao-Yu ZhangDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, PR China; ;Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, PR China;
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Xi LiDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, PR China; ;Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, PR China; ;Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, PR China;
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Xiao-Qing YuanDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, PR China; ;Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, PR China;
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Yong-Long YangHaikou People's Hospital and Affiliated Haikou Hospital of Xiangya Medical School, Central South University, Haikou, PR China;
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Ke-Wei ZhuDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, PR China; ;Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, PR China;
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Hui ZengDepartment of Hematology, Xiangya Hospital, Central South University, Changsha, PR China
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Xiao-Lin LiDepartment of Hematology, Xiangya Hospital, Central South University, Changsha, PR China
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Shan CaoDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, PR China; ;Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, PR China; ;Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, PR China;
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Hong-Hao ZhouDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, PR China; ;Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, PR China; ;Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, PR China;
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Wei ZhangDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, PR China; ;Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, PR China; ;Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, PR China;
&
Xiao-Ping ChenDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, PR China; ;Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, PR China; ;Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, PR China; Correspondence[email protected]
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Pages 1948-1957 | Received 27 Jun 2016, Accepted 26 Nov 2016, Published online: 12 Dec 2016
 
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Abstract

Whether long non-coding RNA (lncRNA) single-nucleotide polymorphisms (SNPs) affect prognosis of acute myeloid leukemia (AML) remains unknown. To search the association between lncRNA SNPs and AML outcomes, thirty tagSNPs in five lncRNAs were genotyped in 313 AML patients. Survival analysis indicated that GAS5 rs55829688 (T > C) was significantly associated with prognosis of AML (p = 0.018). Patients with rs55829688 CC genotype showed higher GAS5 expression in peripheral blood mononuclear cells (PBMCs) (p = 0.025) and harbored a longer platelets recovery (p = 0.040) than carriers of rs55829688T allele. In vitro study indicated that GAS5 promoter harboring the rs55829688C allele showed marginally increased reporter gene activity (p = 0.019), and the promoter activity was increased by TP63 in a dose-dependent manner (P = 0.001). Moreover, GAS5 higher expression predict shorter AML overall survival (OS), which validated in GEO GSE12417 dataset (p = 0.011). In conclusion, rs55829688 polymorphism could increase GAS5 expression by interacting with TP63, which might aggravate the myelosuppression and in turn lead to poor prognosis in AML. Trail registration number: ChiCTR-PPC-14005297.

Acknowledgements

This project was supported by Chinese National Science Foundation [Nos. 81673518, 81422052, 81403017], Special topic of the major subject of national science and technology [2012ZX09509-339 107], Hunan Provincial Natural Science Foundation of China [13JJ1010], and Funds for Hunan education department program [No. 12K006].

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2016.1266626.

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