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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 Vlambda and 2 VH sequences, each set comprised in the ratio 1:1.5. The 2 VH sequences and 2 Vlambda 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 Vlambda 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.

© 2001 by The American Society of Hematology.
 

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