title: Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia.
abstract: The prognosis of cytogenetically normal acute myeloid leukemia (CN-AML) varies greatly among patients. Achievement of complete remission (CR) after chemotherapy is indispensable for a better prognosis. To develop a gene signature predicting overall survival (OS) in CN-AML, we performed data mining procedure based on whole genome expression data of both blood cancer cell lines and AML patients from open access database. A gene expression signature including 42 probes was derived. These probes were significantly associated with both cytarabine half maximal inhibitory concentration values in blood cancer cell lines and OS in CN-AML patients. By using cox regression analysis and linear regression analysis, a chemo-sensitive score calculated algorithm based on mRNA expression levels of the 42 probes was established. The scores were associated with OS in both the training sample (p=5.13 × 10-4, HR=2.040, 95% CI: 1.364-3.051) and the validation sample (p=0.002, HR=2.528, 95% CI: 1.393-4.591) of the GSE12417 dataset from Gene Expression Omnibus. In The Cancer Genome Atlas (TCGA) CN-AML patients, higher scores were found to be associated with both worse OS (p=0.013, HR=2.442, 95% CI: 1.205-4.950) and DFS (p=0.015, HR=2.376, 95% CI: 1.181-4.779). Results of gene ontology (GO) analysis showed that all the significant GO Terms were correlated with cellular component of mitochondrion. In summary, a novel gene set that could predict prognosis of CN-AML was identified presently, which provided a new way to identify genes impacting AML chemo-sensitivity and prognosis.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, P. R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Diagnostic Radiology, Hunan Cancer Hospital, Changsha 410013, Hunan, P. R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wen
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Tan
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, P. R. China.
authors.forename: Pan
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, P. R. China.
authors.forename: Feng-Mei
authors.initials: FM
authors.lastname: Pang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, P. R. China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, P. R. China.
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, P. R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, P. R. China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000097:blood / Q000494:pharmacology*; D003561:Cytarabine / Q000097:blood / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine
keywords: acute myeloid leukemia; chemosensitivity; cytarabine; prognosis; signature