title: Long non-coding RNA GAS5 polymorphism predicts a poor prognosis of acute myeloid leukemia in Chinese patients via affecting hematopoietic reconstitution.
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.
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , PR China.|b Institute of Clinical Pharmacology, Central South University , Hunan Key Laboratory of Pharmacogenetics , Changsha , PR China.
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , PR China.|b Institute of Clinical Pharmacology, Central South University , Hunan Key Laboratory of Pharmacogenetics , Changsha , PR China.
authors.forename: Dao-Yu
authors.initials: DY
authors.lastname: Zhang
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , PR China.|b Institute of Clinical Pharmacology, Central South University , Hunan Key Laboratory of Pharmacogenetics , Changsha , PR China.|c Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study , Hengyang , PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , PR China.|b Institute of Clinical Pharmacology, Central South University , Hunan Key Laboratory of Pharmacogenetics , Changsha , PR China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Yuan
authors.affiliation: d Haikou People's Hospital and Affiliated Haikou Hospital of Xiangya Medical School, Central South University , Haikou , PR China.
authors.forename: Yong-Long
authors.initials: YL
authors.lastname: Yang
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , PR China.|b Institute of Clinical Pharmacology, Central South University , Hunan Key Laboratory of Pharmacogenetics , Changsha , PR China.
authors.forename: Ke-Wei
authors.initials: KW
authors.lastname: Zhu
authors.affiliation: e Department of Hematology , Xiangya Hospital, Central South University , Changsha , PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
authors.affiliation: e Department of Hematology , Xiangya Hospital, Central South University , Changsha , PR China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Li
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , PR China.|b Institute of Clinical Pharmacology, Central South University , Hunan Key Laboratory of Pharmacogenetics , Changsha , PR China.|c Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study , Hengyang , PR China.
authors.forename: Shan
authors.initials: S
authors.lastname: Cao
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , PR China.|b Institute of Clinical Pharmacology, Central South University , Hunan Key Laboratory of Pharmacogenetics , Changsha , PR China.|c Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study , Hengyang , PR China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , PR China.|b Institute of Clinical Pharmacology, Central South University , Hunan Key Laboratory of Pharmacogenetics , Changsha , PR China.|c Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study , Hengyang , PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , PR China.|b Institute of Clinical Pharmacology, Central South University , Hunan Key Laboratory of Pharmacogenetics , Changsha , PR China.|c Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study , Hengyang , PR China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor; D002681:China; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D005838:Genotype; D006410:Hematopoiesis / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D062085:RNA, Long Noncoding / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C561567:GAS5 long non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: Growth arrest specific 5; acute myeloid leukemia; long non-coding RNA; promoter; single nucleotide polymorphism