@article{Dirk Kienle_Axel Benner_Carolin Läufle_Dirk Winkler_Christof Schneider_Andreas Bühler_Thorsten Zenz_Annett Habermann_Ulrich Jäger_Peter Lichter_Riccardo Dalla-Favera_Hartmut Döhner_Stephan Stilgenbauer_2010, place={Pavia, Italy}, title={Gene expression factors as predictors of genetic risk and survival in chronic lymphocytic leukemia}, volume={95}, url={https://haematologica.org/article/view/5454}, DOI={10.3324/haematol.2009.010298}, abstractNote={<strong>Background</strong> 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 (<em>IGHV</em> status, genomic abnormalities).<strong>Design and Methods</strong> Expression markers were evaluated using real-time quantitative reverse transcriptase polymerase chain reaction in CD19<sup>+</sup>-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.<strong>Results</strong> For individual markers, <em>ZAP70</em> expression provided the highest rate (81%) of correct assignment of patients at genetic risk (<em>IGHV</em> unmutated, V3-21 usage, 11q- or 17p-), followed by <em>LPL</em> and <em>TCF7</em> (76% both). The assignment rate was improved to 88% by information from a four-gene combination (<em>ZAP70, TCF7, DMD, ATM</em>). In multivariate analysis of treatment-free survival, <em>IGHV</em> mutation status and expression of <em>ADAM29</em> were of independent prognostic value besides disease stage. With regards to overall survival, expression of <em>ATM</em>, <em>ADAM29</em>, <em>TCL1</em>, and <em>SEPT10</em> provided prognostic information in addition to that derived from clinical and genetic factors.<strong>Conclusions</strong&gt; 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.}, number={1}, journal={Haematologica}, author={Dirk Kienle and Axel Benner and Carolin Läufle and Dirk Winkler and Christof Schneider and Andreas Bühler and Thorsten Zenz and Annett Habermann and Ulrich Jäger and Peter Lichter and Riccardo Dalla-Favera and Hartmut Döhner and Stephan Stilgenbauer}, year={2010}, month={Jan.}, pages={102-109} }