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, Thomas Elmer Witzig, Grzegorz S Nowakowski, Clive S. Zent, Tim G. Call, Betsy LaPlant, Gordon W. Dewald, Diane F Jelinek, Neil Elliot Kay

Research output: Contribution to journalArticle

106 Citations (Scopus)

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

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B-Cell Chronic Lymphocytic Leukemia
Survival
Observational Studies
Therapeutics
Fluorescence In Situ Hybridization
Fibronectins
Cytogenetics
Cell Communication
Anti-Idiotypic Antibodies
Flow Cytometry
B-Lymphocytes
Cohort Studies
Multivariate Analysis
Prospective Studies
Apoptosis
Mutation
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

CD49d expression is an independent predictor of overall survival in patients with chronic lymphocytic leukaemia : A prognostic parameter with therapeutic potential. / Shanafelt, Tait D.; Geyer, Susan M.; Bone, Nancy D.; Tschumper, Renee C.; Witzig, Thomas Elmer; Nowakowski, Grzegorz S; Zent, Clive S.; Call, Tim G.; LaPlant, Betsy; Dewald, Gordon W.; Jelinek, Diane F; Kay, Neil Elliot.

In: British Journal of Haematology, Vol. 140, No. 5, 03.2008, p. 537-546.

Research output: Contribution to journalArticle

Shanafelt, Tait D. ; Geyer, Susan M. ; Bone, Nancy D. ; Tschumper, Renee C. ; Witzig, Thomas Elmer ; Nowakowski, Grzegorz S ; Zent, Clive S. ; Call, Tim G. ; LaPlant, Betsy ; Dewald, Gordon W. ; Jelinek, Diane F ; Kay, Neil Elliot. / CD49d expression is an independent predictor of overall survival in patients with chronic lymphocytic leukaemia : A prognostic parameter with therapeutic potential. In: British Journal of Haematology. 2008 ; Vol. 140, No. 5. pp. 537-546.
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AU - Shanafelt, Tait D.

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AU - Bone, Nancy D.

AU - Tschumper, Renee C.

AU - Witzig, Thomas Elmer

AU - Nowakowski, Grzegorz S

AU - Zent, Clive S.

AU - Call, Tim G.

AU - LaPlant, Betsy

AU - Dewald, Gordon W.

AU - Jelinek, Diane F

AU - Kay, Neil Elliot

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AB - 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.

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