Clonal evolution in Waldenstrom macroglobulinemia highlights functional role of B-cell receptor

Bogoljub Ciric, Virginia VanKeulen, Moses Rodriguez, Robert A. Kyle, Morie A. Gertz, Larry R. Pease

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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

Original languageEnglish (US)
Pages (from-to)321-323
Number of pages3
Issue number1
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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