title: Cell surface phenotype profiles distinguish stable and progressive chronic lymphocytic leukemia.
abstract: Chronic lymphocytic leukemia (CLL) is clinically heterogeneous. While some patients have indolent disease for many years, 20-30% will progress and ultimately die of their disease. CLL may be classified by the Rai or Binet staging system, mutational status of the immunoglobulin variable heavy-chain gene (IGVH), ZAP-70 overexpression, cytogenetic abnormalities (13q-, + 12, 11q-, 17p-) and expression of several cell surface antigens (CD38, CD49d) that correlate with risk of disease progression. However, none of these markers identify all cases of CLL at risk. In a recent review, we summarized those CD antigens known to correlate with the prognosis of CLL. The present study has identified surface profiles of CD antigens that distinguish clinically progressive CLL from slow-progressive and stable CLL. Using an extended DotScan(™) CLL antibody microarray (Version 3; 182 CD antibodies), and with refined analysis of purified CD19 + B-cells, the following 27 CD antigens were differentially abundant for progressive CLL: CD11a, CD11b, CD11c, CD18, CD19, CD20 (two epitopes), CD21, CD22, CD23, CD24, CD25, CD38, CD40, CD43, CD45, CD45RA, CD52, CD69, CD81, CD84, CD98, CD102, CD148, CD180, CD196 and CD270. The extensive surface profiles obtained provide disease signatures with an accuracy of 79.2%, a sensitivity of 83.9% and a specificity of 72.5% that could provide the basis for a rapid test to triage patients with CLL according to probability of clinical progression and potential earlier requirement for treatment.
authors.affiliation: School of Molecular Bioscience, University of Sydney , Sydney, NSW , Australia.
authors.forename: Pauline Y
authors.initials: PY
authors.lastname: Huang
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Best
authors.forename: Juhura G
authors.initials: JG
authors.lastname: Almazi
authors.forename: Larissa
authors.initials: L
authors.lastname: Belov
authors.forename: Zadie A
authors.initials: ZA
authors.lastname: Davis
authors.forename: Aneela
authors.initials: A
authors.lastname: Majid
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Dana
authors.initials: D
authors.lastname: Pascovici
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Mulligan
authors.forename: Richard I
authors.initials: RI
authors.lastname: Christopherson
mesh_terms: D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D018450:Disease Progression; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D011379:Prognosis; D015203:Reproducibility of Results
chemical_list: D000954:Antigens, Surface
keywords: CD antigens; Chronic lymphocytic leukemia; antibody microarray; immunophenotype; prognosis