title: Complement cascade gene expression defines novel prognostic subgroups of acute myeloid leukemia.
abstract: The involvement of the complement pathway in cancer is supported by a growing body of evidence, and yet its role in acute myeloid leukemia (AML) has not been extensively studied. We examined the expression of 87 genes in the complement, coagulation, and fibrinolysis-proteolytic pathways in 374 cytogenetically normal AML samples and observed that these samples can be divided into subgroups on the basis of complement gene expression. Three complement regulatory genes were linked to poor outcome as individual factors in a multivariate analysis (CFH, CFD, and SERPING1) in multiple cohorts. The combined expression of these genes was significantly associated with poorer overall survival in two cohorts of patients <60 years of age, independent of other factors (p ≤ 0.0004). For patients with an intermediate molecular risk, this three-gene risk marker enabled stratification of patients into prognostic subgroups with survival ranging from 17.4% to 44.1%. Thus, the expression of complement pathway genes is linked to outcome in AML, and a three-gene risk marker may improve the risk assessment of patients.
authors.affiliation: Research Institute of the McGill University Health Centre and McGill University, Montreal, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Laverdière
authors.affiliation: Research Institute of the McGill University Health Centre and McGill University, Montreal, Canada.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Boileau
authors.affiliation: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Herold
authors.affiliation: Research Institute of the McGill University Health Centre and McGill University, Montreal, Canada.
authors.forename: Janusz
authors.initials: J
authors.lastname: Rak
authors.affiliation: Department of Medicine, Hematology and Oncology, University of Münster, Münster, Germany.
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.affiliation: Department of Medicine, Hematology, Oncology, Tumor Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wörmann
authors.affiliation: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.affiliation: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), Munich, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Spiekermann
authors.affiliation: Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Bohlander
authors.affiliation: Research Institute of the McGill University Health Centre and McGill University, Montreal, Canada. Electronic address: kolja.eppert@mcgill.ca.
authors.forename: Kolja
authors.initials: K
authors.lastname: Eppert
mesh_terms: D000293:Adolescent; D000328:Adult; D016000:Cluster Analysis; D015331:Cohort Studies; D030561:Databases, Nucleic Acid; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D053263:Gene Regulatory Networks; D006801:Humans; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D059467:Transcriptome; D055815:Young Adult