title: Gene expression of INPP5F as an independent prognostic marker in fludarabine-based therapy of chronic lymphocytic leukemia.
abstract: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Various disease-related and patient-related factors have been shown to influence the course of the disease. The aim of this study was to identify novel biomarkers of significant clinical relevance. Pretreatment CD19-separated lymphocytes (n=237; discovery set) and peripheral blood mononuclear cells (n=92; validation set) from the REACH trial, a randomized phase III trial in relapsed CLL comparing rituximab plus fludarabine plus cyclophosphamide with fludarabine plus cyclophosphamide alone, underwent gene expression profiling. By using Cox regression survival analysis on the discovery set, we identified inositol polyphosphate-5-phosphatase F (INPP5F) as a prognostic factor for progression-free survival (P<0.001; hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.35-1.98) and overall survival (P<0.001; HR, 1.47; 95% CI, 1.18-1.84), regardless of adjusting for known prognostic factors. These findings were confirmed on the validation set, suggesting that INPP5F may serve as a novel, easy-to-assess future prognostic biomarker for fludarabine-based therapy in CLL.
authors.affiliation: Roche Pharma Research and Early Development, Innovation Center, Basel, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Palermo
authors.affiliation: Roche Pharma Research and Early Development, Innovation Center, Penzberg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Maisel
authors.affiliation: Hoffman-La Roche Pharmaceuticals Ltd, Welwyn, UK.
authors.forename: M
authors.initials: M
authors.lastname: Barrett
authors.affiliation: Hoffman-La Roche Ltd, Basel, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Smith
authors.affiliation: Roche Pharma Research and Early Development, Innovation Center, Basel, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Duchateau-Nguyen
authors.affiliation: Roche Pharma Research and Early Development, Innovation Center, Basel, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Biostatistics, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: R-F
authors.initials: RF
authors.lastname: Yeh
authors.affiliation: Laboratory for Leukemia Diagnostics, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dufour
authors.affiliation: Department of Haematology, Medical University, Lodz, Poland, South San Francisco, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Robak
authors.affiliation: Research Oncology Diagnostics, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Dornan
authors.affiliation: Roche Pharma Research and Early Development, Innovation Center, Penzberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Weisser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D059467:Transcriptome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010744:Phosphoric Monoester Hydrolases; C000606431:INPP5F protein, human; D000072181:Inositol Polyphosphate 5-Phosphatases; D014740:Vidarabine; C024352:fludarabine