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

Aneela Majid, Thet Thet Lin, Giles Best, Keith Fishlock, Saman Hewamana, Guy Pratt, Deborah Yallop, A.G.S Buggins, Simon Wagner, Ben Kennedy, Fiona Miall, Robert Hills, Stephen Devereux, David Oscier, Martin J.S Dyer, Chris Fegan, Chris Pepper

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)


The world of chronic lymphocytic leukemia (CLL) research is awash with prognostic markers. 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 prognostic marker 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 independent prognostic significance in multivariate analysis. In contrast to previous studies, we showed no correlation between CD49d expression 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.
Original languageEnglish
Pages (from-to)750-756
Number of pages7
JournalLeukaemia Research
Issue number6
Early online date18 Nov 2010
Publication statusPublished - Jun 2011
Externally publishedYes


  • CD49d
  • CLL
  • CXCR4
  • Prognosis


Dive into the research topics of 'CD49d is an independent prognostic marker that is associated with CXCR4 expression in CLL.'. Together they form a unique fingerprint.

Cite this