title: Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia.
abstract: To evaluate the prognostic value of genetic mutations for acute myeloid leukemia (AML) patients, we examined the gene status for both fusion products such as AML1 (CBFα)-ETO, CBFβ-MYH11, PML-RARα, and MLL rearrangement as a result of chromosomal translocations and mutations in genes including FLT3, C-KIT, N-RAS, NPM1, CEBPA, WT1, ASXL1, DNMT3A, MLL, IDH1, IDH2, and TET2 in 1185 AML patients. Clinical analysis was mainly carried out among 605 cases without recognizable karyotype abnormalities except for 11q23. Of these 605 patients, 452 (74.7%) were found to have at least 1 mutation, and the relationship of gene mutations with clinical outcome was investigated. We revealed a correlation pattern among NPM1, DNMT3A, FLT3, IDH1, IDH2, CEBPA, and TET2 mutations. Multivariate analysis identified DNMT3A and MLL mutations as independent factors predicting inferior overall survival (OS) and event-free survival (EFS), whereas biallelic CEBPA mutations or NPM1 mutations without DNMT3A mutations conferred a better OS and EFS in both the whole group and among younger patients < 60 years of age. The use of molecular markers allowed us to subdivide the series of 605 patients into distinct prognostic groups with potential clinical relevance.
authors: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai, China.
authors: Yang
authors: Y
authors: Shen
authors: Yong-Mei
authors: YM
authors: Zhu
authors: Xing
authors: X
authors: Fan
authors: Jing-Yi
authors: JY
authors: Shi
authors: Qin-Rong
authors: QR
authors: Wang
authors: Xiao-Jing
authors: XJ
authors: Yan
authors: Zhao-Hui
authors: ZH
authors: Gu
authors: Yan-Yan
authors: YY
authors: Wang
authors: Bing
authors: B
authors: Chen
authors: Chun-Lei
authors: CL
authors: Jiang
authors: Han
authors: H
authors: Yan
authors: Fei-Fei
authors: FF
authors: Chen
authors: Hai-Min
authors: HM
authors: Chen
authors: Zhu
authors: Z
authors: Chen
authors: Jie
authors: J
authors: Jin
authors: Sai-Juan
authors: SJ
authors: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D005819:Genetic Markers; D005820:Genetic Testing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D055815:Young Adult
chemical_list: C000717967:DNMT3A protein, human; D005819:Genetic Markers; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D000090243:Nucleophosmin; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A