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Blood, 1 January 2001, Vol. 97, No. 1, pp. 321-323
BRIEF REPORT
Clonal evolution in Waldenstrom macroglobulinemia highlights
functional role of B-cell receptor
Bogoljub Ciric,
Virginia VanKeulen,
Moses Rodriguez,
Robert A. Kyle,
Morie A. Gertz, and
Larry R. Pease
From the Department of Immunology, Mayo Medical and
Graduate School, Rochester; Division of Hematology and Internal
Medicine, Mayo Clinic, Rochester, MN.
The course of clonal evolution of 2 related clones in the
blood of a patient with Waldenstrom macroglobulinemia (WM) indicates the functional importance for the expression of the B-cell receptor for
the survival of these malignant cells. Protein and nucleotide sequencing of the paraproteins' variable regions revealed 2 predominant V and 2 VH sequences, each set comprised in the
ratio 1:1.5. The 2 VH sequences and 2 V sequences shared the same
VDJ and VJ junctional sequences, respectively, indicating that
2 malignant clones had evolved from a common ancestor. This is the
first report on intraclonal heterogeneity in WM. Comparison of the V
and VH sequences with the closest matching known germline genes showed that they contained approximately 10 somatic mutations each. The distribution and type of mutations demonstrate that mutations have
continued to accumulate in the malignant clones and that selection has
been operating to preserve immunoglobulin structure.
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