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

Tait D. Shanafelt, Susan M. Geyer, Nancy D. Bone, Renee C. Tschumper, Tom E. Witzig, Greg S. Nowakowski, Clive S. Zent, Tim G. Call, Betsy LaPlant, Gordon W. Dewald, Diane F. Jelinek, Neil E. Kay

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)537-546
Number of pages10
JournalBritish journal of haematology
Volume140
Issue number5
DOIs
StatePublished - Mar 2008

Keywords

  • CD49d
  • Chronic lymphocytic leukaemia
  • Prognostic factors
  • Stromal cells
  • Therapy

ASJC Scopus subject areas

  • Hematology

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