Weisser, Martin, Yeh, Ru-Fang, Duchateau-Nguyen, Guillemette, Palermo, Giuseppe, Shi, Xiaoyan, Stinson, Susanna Y., Yu, Nancy, Dufour, Annika, Robak, Tadeusz, Salogub, Galina N., Dmoszynska, Anna, Solal-Celigny, Philippe, Warzocha, Krzysztof ORCID: 0000-0002-2396-3905, Loscertales, Javier, Catalano, John, Larratt, Loree, Rossiev, Viktor A., Bence-Bruckler, Isabelle, Geisler, Christian H., Montillo, Marco, Fischer, Kirsten, Fink, Anna-Maria, Hallek, Michael, Bloehdorn, Johannes, Busch, Raymonde, Benner, Axel, Doehner, Hartmut, Valente, Nancy, Wenger, Michael K., Stilgenbauer, Stephan and Dornan, David (2014). PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia. Blood, 124 (3). S. 420 - 426. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 1528-0020

Full text not available from this repository.

Abstract

Addition of rituximab (R) to fludarabine and cyclophosphamide (FC) has significantly improved patient outcomes in chronic lymphocytic leukemia (CLL). Whether baseline gene expression can identify patients who will benefit from immunochemotherapy over chemotherapy alone has not been determined. We assessed genome-wide expression of 300 pretreatment specimens from a subset of 552 patients in REACH, a study of FC or R-FC in relapsed CLL. An independent test set was derived from 282 pretreatment specimens from CLL8, a study of FC or R-FC in treatment-naive patients. Genes specific for benefit from R-FC were determinedby assessing treatment-gene interactions in Cox proportional hazards models. REACH patients with higher pretreatment protein tyrosine kinase 2 (PTK2) messenger RNA levels derived greater benefit from R-FC, with significant improvements in progression-free survival, independent of known prognostic factors in a multivariate model. Examination of PTK2 gene expression in CLL8 patients yielded similar results. Furthermore, PTK2 inhibition blunted R-dependent cell death in vitro. This retrospective analysis from 2 independent trials revealed that increased PTK2 expression is associated with improved outcomes for CLL patients treated with R-FC vs FC. PTK2 expression may be a useful biomarker for patient selection in future trials. These trials were registered at www.clinicaltrials.gov as #NCT00090051 (REACH) and #NCT00281918 (CLL8).

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Weisser, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yeh, Ru-FangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duchateau-Nguyen, GuillemetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palermo, GiuseppeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shi, XiaoyanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stinson, Susanna Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yu, NancyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dufour, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robak, TadeuszUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salogub, Galina N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dmoszynska, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Solal-Celigny, PhilippeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Warzocha, KrzysztofUNSPECIFIEDorcid.org/0000-0002-2396-3905UNSPECIFIED
Loscertales, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Catalano, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Larratt, LoreeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rossiev, Viktor A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bence-Bruckler, IsabelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geisler, Christian H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montillo, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, KirstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fink, Anna-MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bloehdorn, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Busch, RaymondeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benner, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doehner, HartmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Valente, NancyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wenger, Michael K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stilgenbauer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dornan, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-433818
DOI: 10.1182/blood-2013-12-538975
Journal or Publication Title: Blood
Volume: 124
Number: 3
Page Range: S. 420 - 426
Date: 2014
Publisher: AMER SOC HEMATOLOGY
Place of Publication: WASHINGTON
ISSN: 1528-0020
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FOCAL-ADHESION KINASE; NON-HODGKINS-LYMPHOMA; MEDIATED CELL-DEATH; MONOCLONAL-ANTIBODY; IN-VITRO; RITUXIMAB; CYCLOPHOSPHAMIDE; FLUDARABINE; COMPLEMENT; CANCERMultiple languages
HematologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43381

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item