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Common clonal origin of chronic lymphocytic leukemia and high-grade lymphoma of Richter's syndrome.

Abstract
Patients with B-cell chronic lymphocytic leukemia (CLL) infrequently may develop high-grade B-cell lymphoma, or Richter's syndrome lymphoma (RS lymphoma). Such lymphomas differ from the original leukemia in both histology and clinical behavior. Studies seeking to define the clonal relationship between the cells of the two malignancies in any one patient have yielded conflicting reports. We examined the clonal relationship between the early and late neoplastic cells of a patient who underwent Richter's transformation. In contrast to the original leukemia cells, the secondary high-grade lymphoma was CD5-. However, both the leukemia cells and the evolved RS lymphoma expressed surface IgM lambda reactive with Lc1, a murine monoclonal antibody specific for a supratypic cross-reactive idiotype encoded by a subset of human Ig variable region genes of the VH4 subgroup. Nucleic acid sequence analyses of the heavy and light chain variable region genes expressed by both leukemia and lymphoma cells show that the CD5- B-cell lymphoma constitutes a clonal expansion of mutant cells derived from the original CD5+ B-cell leukemia. Moreover, certain sets of somatic mutations distinguish the Ig variable region genes used by RS lymphoma from those expressed by the CLL B cells. This is the first study to establish the clonal relationship between CLL and RS lymphoma through primary structural analyses of the expressed Ig genes.
AuthorsV Cherepakhin, S M Baird, G W Meisenholder, T J Kipps
JournalBlood (Blood) Vol. 82 Issue 10 Pg. 3141-7 (Nov 15 1993) ISSN: 0006-4971 [Print] United States
PMID7693038 (Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, CD
  • CD5 Antigens
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
Topics
  • Amino Acid Sequence
  • Antigens, CD (analysis)
  • Base Sequence
  • CD5 Antigens
  • Genes, Immunoglobulin
  • Humans
  • Immunoglobulin Heavy Chains (genetics)
  • Immunoglobulin Variable Region (genetics)
  • Immunophenotyping
  • Leukemia, Lymphocytic, Chronic, B-Cell (genetics, immunology)
  • Lymphoma, B-Cell (genetics, immunology)
  • Lymphoma, Non-Hodgkin (genetics, immunology)
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Syndrome

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