Dataset Information

Gene expression factors as predictors of genetic risk and survival in chronic lymphocytic leukemia.

ABSTRACT:

Background

A variety of surrogate markers for genetic features and outcome have been described in chronic lymphocytic leukemia based on gene expression analyses. Previous studies mostly focused on individual markers and selected disease characteristics, which makes it difficult to estimate the relative value of the novel markers. Therefore, in the present study a comprehensive approach was chosen investigating 18 promising, partly novel expression markers in a well characterized cohort of patients with long clinical follow-up and full genetic information (IGHV status, genomic abnormalities).

Design and methods

Expression markers were evaluated using real-time quantitative reverse transcriptase polymerase chain reaction in CD19(+)-purified samples from 151 patients. Multivariate analyses were performed to test the markers' ability to identify patients at genetic risk and as prognostic markers in the context of established prognostic factors.

Results

For individual markers, ZAP70 expression provided the highest rate (81%) of correct assignment of patients at genetic risk (IGHV unmutated, V3-21 usage, 11q- or 17p-), followed by LPL and TCF7 (76% both). The assignment rate was improved to 88% by information from a four-gene combination (ZAP70, TCF7, DMD, ATM). In multivariate analysis of treatment-free survival, IGHV mutation status and expression of ADAM29 were of independent prognostic value besides disease stage. With regards to overall survival, expression of ATM, ADAM29, TCL1, and SEPT10 provided prognostic information in addition to that derived from clinical and genetic factors.

Conclusions

Gene expression markers are suitable for screening but not as surrogates for the information from genetic risk factors. While many individual markers may be associated with outcome, only a few are of independent prognostic significance. With regard to prognosis estimation, the genetic prognostic factors cannot be replaced by the expression markers.

SUBMITTER: Kienle D

PROVIDER: S-EPMC2805743 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Publications

Gene expression factors as predictors of genetic risk and survival in chronic lymphocytic leukemia.

Kienle Dirk D Benner Axel A Läufle Carolin C Winkler Dirk D Schneider Christof C Bühler Andreas A Zenz Thorsten T Habermann Annett A Jäger Ulrich U Lichter Peter P Dalla-Favera Riccardo R Döhner Hartmut H Stilgenbauer Stephan S

Haematologica 20091130 1

<h4>Background</h4>A variety of surrogate markers for genetic features and outcome have been described in chronic lymphocytic leukemia based on gene expression analyses. Previous studies mostly focused on individual markers and selected disease characteristics, which makes it difficult to estimate the relative value of the novel markers. Therefore, in the present study a comprehensive approach was chosen investigating 18 promising, partly novel expression markers in a well characterized cohort o ...[more]

PMID: 19951976

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Project description:Previous studies have shown increased familial risk for chronic lymphocytic leukemia. In the most comprehensive study to date, we evaluated risk of chronic lymphocytic leukemia and lymphoproliferative disorders among first-degree relatives of chronic lymphocytic leukemia cases compared to first-degree relatives of controls.Population-based registry data from Sweden were used to evaluate outcomes in 26,947 first-degree relatives of 9,717 chronic lymphocytic leukemia patients (diagnosed 1958-2004) compared with 107,223 first-degree relatives of 38,159 matched controls. Using a marginal survival model, we calculated relative risks (RR) and 95% confidence intervals as measures of familial aggregation.Compared to relatives of controls, relatives of chronic lymphocytic leukemia patients had an increased risk for chronic lymphocytic leukemia (RR=8.5, 6.1-11.7) and other non-Hodgkin's lymphomas (NHLs) (RR=1.9, 1.5-2.3). Evaluating NHL subtypes, we found a striking excess of indolent B-cell NHL, specifically lymphoplasmacytic lymphoma/Waldenström macroglobulinemia and hairy cell leukemia. No excesses of aggressive B-cell or T-cell lymphomas were found. There was no statistical excess of Hodgkin's lymphoma, multiple myeloma, or the precursor condition, monoclonal gammopathy of undetermined significance, among chronic lymphocytic leukemia relatives.These familial aggregations are striking and provide novel clues to research designed to uncover early pathogenetic mechanisms in chronic lymphocytic leukemia including studies to identify germ line susceptibility genes. However, clinicians should counsel their chronic lymphocytic leukemia patients emphasizing that because the baseline population risks are low, the absolute risk for a first-degree relative to develop chronic lymphocytic leukemia or another indolent lymphoma is low. At this time, an increased medical surveillance of first-degree relatives of chronic lymphocytic leukemia patients has no role outside research studies.

Dataset Information

Gene expression factors as predictors of genetic risk and survival in chronic lymphocytic leukemia.

Background

Design and methods

Results

Conclusions

Publications

Gene expression factors as predictors of genetic risk and survival in chronic lymphocytic leukemia.

Similar Datasets

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