title: A 4-gene expression score associated with high levels of Wilms Tumor-1 (WT1) expression is an adverse prognostic factor in acute myeloid leukaemia.
abstract: Wilms Tumor-1 (WT1) expression level is implicated in the prognosis of acute myeloid leukaemia (AML). We hypothesized that a gene expression profile associated with WT1 expression levels might be a good surrogate marker. We identified high WT1 gene sets by comparing the gene expression profiles in the highest and lowest quartiles of WT1 expression in two large AML studies. Two high WT1 gene sets were found to be highly correlated in terms of the altered genes and expression profiles. We identified a 17-probe set signature of the high WT1 set as the optimal prognostic predictor in the first AML set, and showed that it was able to predict prognosis in the second AML series after adjustment for European LeukaemiaNet genetic groups. The gene signature also proved to be of prognostic value in a third AML series of 163 samples assessed by RNA sequencing, demonstrating its cross-platform consistency. This led us to derive a 4-gene expression score, which faithfully predicted adverse outcome. In conclusion, a short gene signature associated with high WT1 expression levels and the resultant 4-gene expression score were found to be predictive of adverse prognosis in AML. This study provides new clues to the molecular pathways underlying high WT1 states in leukaemia.
authors.affiliation: Digestive Oncology Research Center, Digestive Disease Research Institute (DDRI), Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.|Haematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom.
authors.forename: Ahmadreza
authors.initials: A
authors.lastname: Niavarani
authors.affiliation: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Herold
authors.affiliation: Department of Haematology, University College London Hospitals NHS Trust, London, UK.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Reyal
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.|Department of Medicine A - Haematology, Oncology and Pneumology, University of Münster, Münster, Germany.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Sauerland
authors.affiliation: Department of Molecular Medicine and Pathology, The University of Auckland, Auckland, New Zealand.
authors.forename: Thomas
authors.initials: T
authors.lastname: Buchner
authors.affiliation: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.affiliation: Department of Molecular Medicine and Pathology, The University of Auckland, Auckland, New Zealand.
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Bohlander
authors.affiliation: Department of Haematology, Erasmus University Medical Centre Cancer Institute, Rotterdam, the Netherlands.
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Valk
authors.affiliation: Haematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnet
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D016162:Genes, Wilms Tumor; D005819:Genetic Markers; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D025721:WT1 Proteins / Q000097:blood* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: AML; WT1; expression score; gene signature; prognosis