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@ARTICLE{Weisser:128518,
author = {M. Weisser and R.-F. Yeh and G. Duchateau-Nguyen and G.
Palermo and T. Q. Nguyen and X. Shi and S. Y. Stinson and N.
Yu and A. Dufour and T. Robak and G. N. Salogub and A.
Dmoszynska and P. Solal-Celigny and K. Warzocha and J.
Loscertales and J. Catalano and L. Larratt and V. A. Rossiev
and I. Bence-Bruckler and C. H. Geisler and M. Montillo and
K. Fischer and A.-M. Fink and M. Hallek and J. Bloehdorn and
R. Busch and A. Benner$^*$ and H. Döhner and N. Valente and
M. K. Wenger and S. Stilgenbauer and D. Dornan},
title = {{PTK}2 expression and immunochemotherapy outcome in chronic
lymphocytic leukemia.},
journal = {Blood},
volume = {124},
number = {3},
issn = {1528-0020},
address = {Stanford, Calif.},
publisher = {HighWire Press},
reportid = {DKFZ-2017-04534},
pages = {420 - 425},
year = {2014},
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-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).},
keywords = {Antibodies, Monoclonal, Murine-Derived (NLM Chemicals) /
RNA, Messenger (NLM Chemicals) / RNA, Neoplasm (NLM
Chemicals) / Rituximab (NLM Chemicals) / Cyclophosphamide
(NLM Chemicals) / Focal Adhesion Kinase 1 (NLM Chemicals) /
PTK2 protein, human (NLM Chemicals) / Vidarabine (NLM
Chemicals) / fludarabine (NLM Chemicals)},
cin = {C060},
ddc = {610},
cid = {I:(DE-He78)C060-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24916506},
doi = {10.1182/blood-2013-12-538975},
url = {https://inrepo02.dkfz.de/record/128518},
}