title: Inherited predisposition to CLL is detectable as subclinical monoclonal B-lymphocyte expansion.
abstract: Monoclonal chronic lymphocytic leukemia (CLL)-phenotype cells are detectable in 3.5% of otherwise healthy persons using flow cytometric analysis of CD5/CD20/CD79b expression on CD19-gated B cells. To determine whether detection of such CLL-phenotype cells is indicative of an inherited predisposition, we examined 59 healthy, first-degree relatives of patients from 21 families with CLL. CLL-phenotype cells were detected in 8 of 59 (13.5%) relatives, representing a highly significant increase in risk (P =.00002). CLL-phenotype cell levels were stable with time and had the characteristics of indolent CLL. Indolent and aggressive clinical forms were found in family members, suggesting that initiation and proliferation involves distinct factors. The detection of CLL-phenotype cells provides a surrogate marker of carrier status, potentially facilitating gene identification through mapping in families and direct analysis of isolated CLL-phenotype cells.
authors.affiliation: Academic Unit of Haematology and Oncology, University of Leeds, HMDS, West Yorkshire, Surrey, United Kingdom.
authors.forename: Andy C
authors.initials: AC
authors.lastname: Rawstron
authors.forename: Martin R
authors.initials: MR
authors.lastname: Yuille
authors.forename: Julie
authors.initials: J
authors.lastname: Fuller
authors.forename: Matthew
authors.initials: M
authors.lastname: Cullen
authors.forename: Ben
authors.initials: B
authors.lastname: Kennedy
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Richards
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Jack
authors.forename: Estella
authors.initials: E
authors.lastname: Matutes
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D015995:Prevalence
chemical_list: D015703:Antigens, CD