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Clinical Trial
. 2015 Oct 2;5(10):e353.
doi: 10.1038/bcj.2015.82.

Gene Expression of INPP5F as an Independent Prognostic Marker in Fludarabine-Based Therapy of Chronic Lymphocytic Leukemia

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Free PMC article
Clinical Trial

Gene Expression of INPP5F as an Independent Prognostic Marker in Fludarabine-Based Therapy of Chronic Lymphocytic Leukemia

G Palermo et al. Blood Cancer J. .
Free PMC article

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.

Conflict of interest statement

GP, DM, MB, HS, GD-N, TN, R-FY and MW are employees of F Hoffmann-La Roche Ltd. TR received research funding and honoraria from F Hoffmann-La Roche Ltd. AD and DD declare no conflict of interest.

Figures

Figure 1
Figure 1
The mRNA isolated from: (a) CD19+-separated samples and (b) PBMCs. Kaplan–Meier curves of PFS stratified by INPP5F expression levels (red: high INPP5F expression, above the median; blue: low INPP5F expression, below the median).
Figure 2
Figure 2
The mRNA isolated from: (a) CD19+-separated samples and (b) PBMCs. Kaplan–Meier curves of OS stratified by INPP5F expression levels (red: high INPP5F expression, above the median; blue: low INPP5F expression, below the median).
Figure 3
Figure 3
Data set from Herold et al. Kaplan–Meier curves of OS stratified by INPP5F expression levels (red: high INPP5F expression, above the median; blue: low INPP5F expression, below the median).

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