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

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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
JournalBlood
Volume97
Issue number1
DOIs
StatePublished - Jan 1 2001

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Clonal Evolution
Waldenstrom Macroglobulinemia
B-Lymphocytes
Clone Cells
Cells
Paraproteins
Mutation
Immunoglobulins
Blood
Nucleotides
Genes
Protein Sequence Analysis
Cell Survival
Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

Clonal evolution in Waldenstrom macroglobulinemia highlights functional role of B-cell receptor. / Ciric, Bogoljub; VanKeulen, Virginia; Rodriguez, Moses; Kyle, Robert A.; Gertz, Morie; Pease, Larry R.

In: Blood, Vol. 97, No. 1, 01.01.2001, p. 321-323.

Research output: Contribution to journalArticle

Ciric, Bogoljub ; VanKeulen, Virginia ; Rodriguez, Moses ; Kyle, Robert A. ; Gertz, Morie ; Pease, Larry R. / Clonal evolution in Waldenstrom macroglobulinemia highlights functional role of B-cell receptor. In: Blood. 2001 ; Vol. 97, No. 1. pp. 321-323.
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