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CD49d expression is an independent predictor of overall survival in patients with chronic lymphocytic leukaemia: a prognostic parameter with therapeutic potential

CD49d expression is an independent predictor of overall survival in patients with chronic... In vitro studies have demonstrated that surface expression of CD49d on chronic lymphocytic leukaemia (CLL) B cells facilitates leukaemic cell–stromal interactions by binding to fibronectin. This interaction reduces both spontaneous and drug‐induced apoptosis. The present study measured CD49d expression by flow cytometry in a cohort of untreated CLL patients previously accrued to a prospective observational study and evaluated the relationship with overall survival (OS). Among the 158 CLL patients tested, the percentage of leukaemic B cells expressing CD49d ranged from 0 to 100%. When all risk factors were treated as continuous variables, CD49d expression showed moderate correlation with expression of ZAP‐70 (r = 0·54; P < 0·0001) and CD38 (r = 0·58; P < 0·0001) but not %IGHV mutation. As a continuous variable, CD49d expression strongly correlated with OS (P < 0·0001). Recursive partitioning analysis suggested the 45% threshold of CD49d expression best predicted OS. Multivariate analysis, controlling for disease stage, ZAP‐70, IGHV status and fluorescent in situ hybridization defects identified CD49d as an independent predictor of OS and was a better predictor of clinical outcome than ZAP‐70, IGHV, or cytogenetics. This observational cohort study suggests that CLL B‐cell expression of CD49d is an easily measurable and independent predictor of OS and CD49d expression in CLL. Importantly, anti‐CD49d antibodies are already approved for treatment of other human diseases. Clinical testing of anti‐CD49d therapy in CLL appears warranted. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Haematology Wiley

CD49d expression is an independent predictor of overall survival in patients with chronic lymphocytic leukaemia: a prognostic parameter with therapeutic potential

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References (64)

Publisher
Wiley
Copyright
"Copyright © 2008 Wiley Subscription Services, Inc., A Wiley Company"
ISSN
0007-1048
eISSN
1365-2141
DOI
10.1111/j.1365-2141.2007.06965.x
pmid
18275431
Publisher site
See Article on Publisher Site

Abstract

In vitro studies have demonstrated that surface expression of CD49d on chronic lymphocytic leukaemia (CLL) B cells facilitates leukaemic cell–stromal interactions by binding to fibronectin. This interaction reduces both spontaneous and drug‐induced apoptosis. The present study measured CD49d expression by flow cytometry in a cohort of untreated CLL patients previously accrued to a prospective observational study and evaluated the relationship with overall survival (OS). Among the 158 CLL patients tested, the percentage of leukaemic B cells expressing CD49d ranged from 0 to 100%. When all risk factors were treated as continuous variables, CD49d expression showed moderate correlation with expression of ZAP‐70 (r = 0·54; P < 0·0001) and CD38 (r = 0·58; P < 0·0001) but not %IGHV mutation. As a continuous variable, CD49d expression strongly correlated with OS (P < 0·0001). Recursive partitioning analysis suggested the 45% threshold of CD49d expression best predicted OS. Multivariate analysis, controlling for disease stage, ZAP‐70, IGHV status and fluorescent in situ hybridization defects identified CD49d as an independent predictor of OS and was a better predictor of clinical outcome than ZAP‐70, IGHV, or cytogenetics. This observational cohort study suggests that CLL B‐cell expression of CD49d is an easily measurable and independent predictor of OS and CD49d expression in CLL. Importantly, anti‐CD49d antibodies are already approved for treatment of other human diseases. Clinical testing of anti‐CD49d therapy in CLL appears warranted.

Journal

British Journal of HaematologyWiley

Published: Mar 1, 2008

Keywords: ; ; ; ;

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