title: High IDH1 expression is associated with a poor prognosis in cytogenetically normal acute myeloid leukemia.
abstract: The prognostic value of IDH1 mutations has been systematically evaluated in acute myeloid leukemia (AML) patients recently. However, the role of IDH1 expression in AML is still under exploration. To investigate the clinical significance, we analyzed the IDH1/2 expression in 320 patients with cytogenetically normal AML (CN-AML) by quantitative real-time reverse-transcription polymerase chain reaction. High expression of IDH1 was predominant in patients with FLT3-ITD and DNMT3A mutations and less prevalent in cases with CEBPA double allele mutations. Strong association was observed between high IDH1 expression and low expression of microRNA 181 family. Prognosis was adversely affected by high IDH1 expression, with shorter overall survival and event-free survival in the context of clinical characteristics, including age, WBC count, and gene mutations of NPM1, FLT3-ITD, CEBPA, IDH1, IDH2 and DNMT3A in CN-AML. Moreover, the clinical outcome of IDH1 expression in terms of overall survival, event-free survival and complete remission rate still remained in multivariate models in CN-AML. Importantly, the prognostic value was validated using the published microarray data from 79 adult patients treated according to the German AMLCG-1999 protocol. Our results demonstrated that high IDH1 expression is associated with a poor prognosis of CN-AML.
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.|Key Laboratory of Hematopoietic Malignancies, Hangzhou, Zhejiang Province, People's Republic of China.|Department of Hematology, The Second Affiliated Hospital of Henan College of Traditional Chinese Medicine, Zhengzhou, China.
authors.forename: Qiu-Ling
authors.initials: QL
authors.lastname: Ma
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.|Key Laboratory of Hematopoietic Malignancies, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Jing-Han
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Yun-Gui
authors.initials: YG
authors.lastname: Wang
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Qi-Tian
authors.initials: QT
authors.lastname: Mu
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Meng-Xia
authors.initials: MX
authors.lastname: Yu
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Wang
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Yin
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Chen
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Sha-Sha
authors.initials: SS
authors.lastname: Lu
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Zhi-Juan
authors.initials: ZJ
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to SJTU School of Medicine and Key Laboratory of Systems Biomedicine Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai, China.
authors.forename: Sai-Juan
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.|Key Laboratory of Hematopoietic Malignancies, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D011379:Prognosis; D016019:Survival Analysis; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C000716967:NPM1 protein, human; D000090243:Nucleophosmin; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: acute myeloid leukemia; gene expression; isocitrate dehydrogenase 1; prognosis