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Frequent somatic mutations in D and/or JH segments of Ig gene in
Waldenstrom's macroglobulinemia and chronic lymphocytic leukemia (CLL) with
Richter's syndrome but not in common CLL
H Aoki, M Takishita, M Kosaka and S Saito
First Department of Internal Medicine, School of Medicine, University of
Tokushima, Japan.
V(D)J recombination and somatic hypermutations are developmentally
regulated during B-cell differentiation; therefore, DNA analysis of the Ig
gene delineates the cellular origin of B-cell neoplasms. We analyzed the
third complementarity-determining region and adjacent regions of the Ig
heavy-chain gene of tumor cells from 7 patients with Waldenstrom's
macroglobulinemia (WM) and from 10 patients with B-cell chronic lymphocytic
leukemia (CLL), 2 of whom progressed to high-grade non-Hodgkin's lymphoma
(NHL), ie, Richter's syndrome (RS). There were no intraclonal variations
resulting from VH replacements or ongoing somatic mutations in both WM and
CLL. We found replacement mutations in the D and/or JH segments in all
patients with WM and in 4 of the 10 patients with CLL, including the 2 RS
patients. Replacement mutations were clustered in codon 102 of the JH
segment. Preferential utilization of the JH4 gene was found in WM (5 of 7
[71.4%]) and in CLL (7 of 10 [70.0%]), and DXP family genes in CLL (5 of 10
[50.0%]). In conclusion, WM and CLL with RS are generated under the
influence of antigenic stimulation and selection. However, the majority of
CLL may arise from a distinct subpopulation that has the restricted
repertoire of nonmutated Ig genes.
Volume 85,
Issue 7,
pp. 1913-1919,
04/01/1995
Copyright © 1995 by The American Society of Hematology
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