title: A two-gene signature, SKI and SLAMF1, predicts time-to-treatment in previously untreated patients with chronic lymphocytic leukemia.
abstract: We developed and validated a two-gene signature that predicts prognosis in previously-untreated chronic lymphocytic leukemia (CLL) patients. Using a 65 sample training set, from a cohort of 131 patients, we identified the best clinical models to predict time-to-treatment (TTT) and overall survival (OS). To identify individual genes or combinations in the training set with expression related to prognosis, we cross-validated univariate and multivariate models to predict TTT. We identified four gene sets (5, 6, 12, or 13 genes) to construct multivariate prognostic models. By optimizing each gene set on the training set, we constructed 11 models to predict the time from diagnosis to treatment. Each model also predicted OS and added value to the best clinical models. To determine which contributed the most value when added to clinical variables, we applied the Akaike Information Criterion. Two genes were consistently retained in the models with clinical variables: SKI (v-SKI avian sarcoma viral oncogene homolog) and SLAMF1 (signaling lymphocytic activation molecule family member 1; CD150). We optimized a two-gene model and validated it on an independent test set of 66 samples. This two-gene model predicted prognosis better on the test set than any of the known predictors, including ZAP70 and serum β2-microglobulin.
authors.affiliation: Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Carmen D
authors.initials: CD
authors.lastname: Schweighofer
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Coombes
authors.forename: Lynn L
authors.initials: LL
authors.lastname: Barron
authors.forename: Lixia
authors.initials: L
authors.lastname: Diao
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Newman
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; C060614:SKI protein, human; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1