Gene expression of INPP5F as an independent prognostic marker in fludarabine-based therapy of chronic lymphocytic leukemia

Blood Cancer J. 2015 Oct 2;5(10):e353. doi: 10.1038/bcj.2015.82.


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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Disease-Free Survival
  • Female
  • Humans
  • Inositol Polyphosphate 5-Phosphatases
  • Kaplan-Meier Estimate
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality
  • Male
  • Middle Aged
  • Phosphoric Monoester Hydrolases / analysis
  • Phosphoric Monoester Hydrolases / biosynthesis*
  • Prognosis
  • Proportional Hazards Models
  • Transcriptome
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Phosphoric Monoester Hydrolases
  • INPP5F protein, human
  • Inositol Polyphosphate 5-Phosphatases
  • Vidarabine
  • fludarabine