title: Non-CLL-like monoclonal B-cell lymphocytosis in the general population: prevalence and phenotypic/genetic characteristics.
abstract: BACKGROUND
  Monoclonal B-cell lymphocytosis (MBL) indicates <5 × 10(9) peripheral blood (PB) clonal B-cells/L in healthy individuals. In most cases, MBL cells show similar phenotypic/genetic features to chronic lymphocytic leukemia cells-CLL-like MBL-but little is known about non-CLL-like MBL.
  
  
  METHODS
  PB samples from 639 healthy individuals (46% men/54% women) >40 years old (62 ± 13 years) with normal lymphocyte counts (2.1 ± 0.7 × 10(9)/L) were immunophenotyped using high-sensitive flow cytometry, based on 8-color stainings and the screening for >5 × 10(6) total PB leukocytes.
  
  
  RESULTS
  Thirteen subjects (2.0%; 9 males/4 females, aged 73 ± 10 years; absolute lymphocyte count: 2.4 ± 0.8 × 10(9)/L) showed a non-CLL-like clonal B-cell population, whose frequency clearly increased with age: 0.4%, 3%, and 5.4% of subjects aged 40-59, 60-79, and ≥80 years, respectively. One single B-cell clone was detected in 9/13 cases, while two B-cell clones were found in 4/13 (n = 17 MBL populations). Nine MBL cell populations showed a CD5(-) phenotype (usually overlapping with marginal zone-derived (MZL) or lymphoplasmacytic (LPL) non-Hodgkin lymphoma (NHL) B-cells, or an unclassifiable NHL), but CD5(-/+d) (n = 3) and CD5(+) (n = 3 non-CLL-like MBL, consistent with a mantle-cell lymphoma (MCL)-like phenotype, and n = 2 CLL-like) MBL were also identified; iFISH supported the diagnosis in most cases. No preferential IGHV usage of B-cell receptor could be found. Twelve cases reevaluated at month +12 showed circulating clonal B-cells, at mean levels significantly higher than those initially detected.
  
  
  CONCLUSIONS
  Non-CLL-like MBL cases frequently show biclonality, in association with MZL-, LPL-, MCL-like, or unclassifiable phenotypic profiles. As with CLL-like MBL, the frequency of non-CLL-like MBL increases with age, with a clear predominance of males.
authors.affiliation: Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer/IBMCC (CSIC-USAL), Salamanca, Spain.
authors.forename: Wendy G
authors.initials: WG
authors.lastname: Nieto
authors.forename: Cristina
authors.initials: C
authors.lastname: Teodosio
authors.forename: Antonio
authors.initials: A
authors.lastname: López
authors.forename: Arancha
authors.initials: A
authors.lastname: Rodríguez-Caballero
authors.forename: Alfonso
authors.initials: A
authors.lastname: Romero
authors.forename: Paloma
authors.initials: P
authors.lastname: Bárcena
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Gutierrez
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Paulino
authors.initials: P
authors.lastname: Fernandez-Navarro
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002999:Clone Cells; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D015995:Prevalence; D012737:Sex Factors; D013030:Spain / Q000453:epidemiology
chemical_list: D007143:Immunoglobulin Heavy Chains