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CD49d is an independent prognostic marker that is associated with CXCR4 expression in CLL

Majid, Aneela, Lin, Thet Thet, Best, Giles, Fishlock, Keith, Hewamana, Saman, Pratt, Guy, Yallop, Deborah, Buggins, Andrea G. S., Wagner, Simon, Kennedy, Ben J., Miall, Fiona, Hills, Robert Kerrin, Devereux, Stephen, Oscier, David G., Dyer, Martin J. S., Fegan, Christopher Daniel and Pepper, Christopher John 2011. CD49d is an independent prognostic marker that is associated with CXCR4 expression in CLL. Leukemia Research 35 (6) , pp. 750-756. 10.1016/j.leukres.2010.10.022

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Abstract

The world of chronic lymphocytic leukemia (CLL) research is awash with prognosticmarkers. However, very few of the current group play a clearly defined role in the pathology of this disease and even fewer represent a tractable therapeutic target. One such marker that fulfils both of these criteria is the integrin CD49d. This molecule been implicated in the capacity of CLL cells to migrate into lymphoid tissues and there is a CD49d blocking antibody, Natalizumab, currently in clinical trials. Here we carried out the largest multi-centre evaluation of CD49d as a prognosticmarker in 652 primary CLL samples. We confirm that CD49d is predictive for time to first treatment (P < 0.0001) and overall survival (P < 0.0001) and increases the prognostic power of CD38, ZAP-70 and IGHV gene mutation status in concordant cases. Furthermore, CD49d retained independentprognostic significance in multivariate analysis. In contrast to previous studies, we showed no correlation between CD49dexpression and in vitro resistance to fludarabine in liquid cultures (P = 0.28) but CD49dhi cells were significantly more resistant than CD49dlo cells when assays were carried out on fibronectin-coated plates (P = 0.03). Furthermore, we showed for the first time that the expression of CD49d is strongly associated with expression of the chemokine receptor CXCR4 suggesting a co-ordinated role for these molecules in the trafficking of CLL cells to the lymphoid tissues. Taken together, our data support the introduction of CD49d into routine immunophenotyping panels for CLL and indicate that the therapeutic targeting of this molecule may prove useful in this disease

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: CD49d; CLL; CXCR4; Prognosis
Publisher: Elsevier
ISSN: 0145-2126
Last Modified: 07 Feb 2019 21:31
URI: http://orca-mwe.cf.ac.uk/id/eprint/25297

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