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Common clonal origin of chronic lymphocytic leukemia and high-grade
lymphoma of Richter's syndrome
V Cherepakhin, SM Baird, GW Meisenholder and TJ Kipps
Department of Medicine-0663, University of California at San Diego, La
Jolla 92093-0663.
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.
Volume 82,
Issue 10,
pp. 3141-3147,
11/15/1993
Copyright © 1993 by The American Society of Hematology
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