TY  - JOUR
AU  - Weisser, Martin
AU  - Yeh, Ru-Fang
AU  - Duchateau-Nguyen, Guillemette
AU  - Palermo, Giuseppe
AU  - Nguyen, Tri Quang
AU  - Shi, Xiaoyan
AU  - Stinson, Susanna Y
AU  - Yu, Nancy
AU  - Dufour, Annika
AU  - Robak, Tadeusz
AU  - Salogub, Galina N
AU  - Dmoszynska, Anna
AU  - Solal-Celigny, Philippe
AU  - Warzocha, Krzysztof
AU  - Loscertales, Javier
AU  - Catalano, John
AU  - Larratt, Loree
AU  - Rossiev, Viktor A
AU  - Bence-Bruckler, Isabelle
AU  - Geisler, Christian H
AU  - Montillo, Marco
AU  - Fischer, Kirsten
AU  - Fink, Anna-Maria
AU  - Hallek, Michael
AU  - Bloehdorn, Johannes
AU  - Busch, Raymonde
AU  - Benner, Axel
AU  - Döhner, Hartmut
AU  - Valente, Nancy
AU  - Wenger, Michael K
AU  - Stilgenbauer, Stephan
AU  - Dornan, David
TI  - PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia.
JO  - Blood
VL  - 124
IS  - 3
SN  - 1528-0020
CY  - Stanford, Calif.
PB  - HighWire Press
M1  - DKFZ-2017-04534
SP  - 420 - 425
PY  - 2014
AB  - 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-naïve patients. Genes specific for benefit from R-FC were determined by 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).
KW  - Antibodies, Monoclonal, Murine-Derived (NLM Chemicals)
KW  - RNA, Messenger (NLM Chemicals)
KW  - RNA, Neoplasm (NLM Chemicals)
KW  - Rituximab (NLM Chemicals)
KW  - Cyclophosphamide (NLM Chemicals)
KW  - Focal Adhesion Kinase 1 (NLM Chemicals)
KW  - PTK2 protein, human (NLM Chemicals)
KW  - Vidarabine (NLM Chemicals)
KW  - fludarabine (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24916506
DO  - DOI:10.1182/blood-2013-12-538975
UR  - https://inrepo02.dkfz.de/record/128518
ER  -