title: A three-gene expression-based risk score can refine the European LeukemiaNet AML classification.
abstract: Risk stratification based on cytogenetics of acute myeloid leukemia (AML) remains imprecise. The introduction of novel genetic and epigenetic markers has helped to close this gap and increased the specificity of risk stratification, although most studies have been conducted in specific AML subpopulations. In order to overcome this limitation, we used a genome-wide approach in multiple AML populations to develop a robust prediction model for AML survival.
  
  
  
  We conducted a genome-wide expression analysis of two data sets from AML patients enrolled into the AMLCG-1999 trial and from the Tumor Cancer Genome Atlas (TCGA) to develop a prognostic score to refine current risk classification and performed a validation on two data sets of the National Taiwan University Hospital (NTUH) and an independent AMLCG cohort.
  
  
  
  In our training set, using a stringent multi-step approach, we identified a small three-gene prognostic scoring system, named Tri-AML score (TriAS) which highly correlated with overall survival (OS). Multivariate analysis revealed TriAS to be an independent prognostic factor in all tested training and additional validation sets, even including age, current cytogenetic-based risk stratification, and three other recently developed expression-based scoring models for AML.
  
  
  
  The Tri-AML score allows robust and clinically practical risk stratification for the outcome of AML patients. TriAS substantially refined current ELN risk stratification assigning 44.5 % of the patients into a different risk category.
authors: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors: Stefan
authors: S
authors: Wilop
authors: Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Wen-Chien
authors: WC
authors: Chou
authors: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors: Edgar
authors: E
authors: Jost
authors: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors: Martina
authors: M
authors: Crysandt
authors: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors: Jens
authors: J
authors: Panse
authors: Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Ming-Kai
authors: MK
authors: Chuang
authors: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors: Tim H
authors: TH
authors: Brümmendorf
authors: Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular, Engineering, University Hospital of the RWTH Aachen, Aachen, Germany.|Institute for Biomedical Engineering - Cell Biology, University Hospital of the RWTH, Aachen, Germany.
authors: Wolfgang
authors: W
authors: Wagner
authors: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Hwei-Fang
authors: HF
authors: Tien
authors: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany. bkharabi@ukaachen.de.
authors: Behzad
authors: B
authors: Kharabi Masouleh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003582:Cytogenetics; D005260:Female; D023281:Genomics; D006801:Humans; D016247:Information Storage and Retrieval / Q000379:methods; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D011379:Prognosis; D018570:Risk Assessment / Q000379:methods*; D000069553:Supervised Machine Learning; D015996:Survival Rate