title: Heterogeneous immunoglobulin gene rearrangement in a B-chronic lymphocytic leukemia progressing into non-Hodgkin lymphoma (Richter syndrome).
abstract: BACKGROUND
  The relationship between chronic lymphocytic leukemia (CLL) and supervening non-Hodgkin lymphoma is debated, as is whether a particular genomic pattern is related to the emergence of the terminal lymphoma. To investigate these features, the molecular organization of the immunoglobulin (Ig) gene region in a case during both the B-CLL and Richter transformation phase was studied.
  
  
  METHODS
  B-CLL and non-Hodgkin lymphoma cells were processed for Southern blot analysis of Ig heavy- and light-chain gene configuration.
  
  
  RESULTS
  Molecular studies of B-CLL cells revealed the presence of a single Ig heavy-chain rearrangement with both kappa and lambda light-chain rearranged genes, which was consistent with the occurrence of multiple mutational events during the development of the B-CLL clone. Molecular analysis of the lymphoma DNA showed new Ig heavy- and kappa light-chain rearrangements in addition to the original ones related to the CLL phase, indicating that the lymphoma tissue consisted of two genotypically distinct populations of cells.
  
  
  CONCLUSIONS
  On the basis of the overall molecular configuration, this heterogeneous pattern of Ig gene rearrangement was interpreted as an inherent genetic instability of the CLL clone, in which multiple mutational events allowed a selective pressure toward more aggressive subclones, resulting in the emergence of the terminal lymphoma.
authors.affiliation: Department of Biomedical Sciences and Human Oncology, University of Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Kerim
authors.forename: M
authors.initials: M
authors.lastname: Geuna
authors.forename: P
authors.initials: P
authors.lastname: Francia di Celle
authors.forename: A
authors.initials: A
authors.lastname: Carbone
authors.forename: R
authors.initials: R
authors.lastname: Ponti
authors.forename: D
authors.initials: D
authors.lastname: Novero
authors.forename: R
authors.initials: R
authors.lastname: Foa
authors.forename: G
authors.initials: G
authors.lastname: Palestro
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013577:Syndrome
chemical_list: D015703:Antigens, CD