title: CD49d expression is an independent predictor of overall survival in patients with chronic lymphocytic leukaemia: a prognostic parameter with therapeutic potential.
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.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. shanafelt.tait@mayo.edu
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
authors.forename: Susan M
authors.initials: SM
authors.lastname: Geyer
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Bone
authors.forename: Renee C
authors.initials: RC
authors.lastname: Tschumper
authors.forename: Tom E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Greg S
authors.initials: GS
authors.lastname: Nowakowski
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.forename: Tim G
authors.initials: TG
authors.lastname: Call
authors.forename: Betsy
authors.initials: B
authors.lastname: Laplant
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Dewald
authors.forename: Diane F
authors.initials: DF
authors.lastname: Jelinek
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D039441:Integrin alpha4 / Q000097:blood*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D039441:Integrin alpha4