title: Combined patterns of IGHV repertoire and cytogenetic/molecular alterations in monoclonal B lymphocytosis versus chronic lymphocytic leukemia.
abstract: BACKGROUND
  Chronic lymphocytic leukemia (CLL)-like monoclonal B lymphocytosis (MBL) with (MBL(hi)) or without (MBL(lo)) absolute B-lymphocytosis precedes most CLL cases,the specific determinants for malignant progression remaining unknown.
  
  
  RESULTS
  For this purpose, simultaneous iFISH and molecular analysis of well-established cytogenetic alterations of chromosomes 11, 12, 13, 14 and 17 together with the pattern of rearrangement of the IGHV genes were performed in CLL-like cells from MBL and CLL cases. Our results based on 78 CLL-like MBL and 117 CLL clones from 166 subjects living in the same geographical area, show the existence of three major groups of clones with distinct but partially overlapping patterns of IGHV gene usage, IGHV mutational status and cytogenetic alterations. These included a group enriched in MBL(lo) clones expressing specific IGHV subgroups (e.g. VH3-23) with no or isolated good-prognosis cytogenetic alterations, a second group which mainly consisted of clinical MBL(hi) and advanced stage CLL with a skewed but different CLL-associated IGHV gene repertoire (e.g. VH1-69), frequently associated with complex karyotypes and poor-prognosis cytogenetic alterations, and a third group of clones with intermediate features, with prevalence of mutated IGHV genes, and higher numbers of del(13q)(+) clonal B-cells.
  
  
  CONCLUSIONS
  These findings suggest that the specific IGHV repertoire and IGHV mutational status of CLL-like B-cell clones may modulate the type of cytogenetic alterations acquired, their rate of acquisition and/or potentially also their clinical consequences. Further long-term follow-up studies investigating the IGHV gene repertoire of MBL(lo) clones in distinct geographic areas and microenvironments are required to confirm our findings and shed light on the potential role of some antigen-binding BCR specificities contributing to clonal evolution.
authors.affiliation: Cancer Research Center, IBMCC, USAL-CSIC, Department of Medicine and Cytometry Service, University of Salamanca and Institute for Biomedical Research of Salamanca, Salamanca, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Henriques
authors.forename: Arancha
authors.initials: A
authors.lastname: Rodríguez-Caballero
authors.forename: Wendy G
authors.initials: WG
authors.lastname: Nieto
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Ignacio
authors.initials: I
authors.lastname: Criado
authors.forename: Quentin
authors.initials: Q
authors.lastname: Lécrevisse
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Maria L
authors.initials: ML
authors.lastname: Pais
authors.forename: Artur
authors.initials: A
authors.lastname: Paiva
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D048429:Cell Size; D002869:Chromosome Aberrations; D002999:Clone Cells; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D025341:Principal Component Analysis; D051881:Receptor, Notch1 / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism
chemical_list: D007143:Immunoglobulin Heavy Chains; D051881:Receptor, Notch1; D011947:Receptors, Antigen, B-Cell