Clonal evolution of B cells in transformation from low- to high-grade lymphoma

András Matolcsy, Elaine J. Schattner, Daniel M. Knowles, Paolo Casali

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


An outcome of low-grade B cell non-Hodgkins's lymphomas is the transformation to high-grade diffuse large B cell lymphomas (DLBL). To investigate the mechanisms of clonal evolution in the transformation to DLBL, we performed longitudinal molecular analyses of immunoglobulin (Ig), V(H)DJ(H) gene sequences expressed in cases of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma (FL) that transformed to DLBL. Among the neoplastic CLL and SLL cells and their respective high-grade transformants, there was no evidence for a clonotypic shift or acquired mutations in the expressed Ig V(H)DJ(H) gene segments, as further confirmed by a specific and sensitive PCR-single strand polymorphism analysis. In contrast, among the FL cells there was a high degree of intraclonal diversification with highly divergent V(H)DJ(H) gene sequences. Despite this intraclonal heterogeneity, the related DLBL expressed a collinear but unique V(H)DJ(H) gene sequence. The intraclonal genealogical tree for the FL case demonstrated that the DLBL emerged in association with unique V(H)DJ(H) gene mutational events. Among the intraclonal FL and related DLBL transformants, the nature and distribution of the Ig V(H)DJ(H) gene mutations were consistent with antigenic selection. Thus, clonal evolution in the transformation from low- to high-grade B cell lymphoma may involve distinct pathways which vary according to the cellular origin and the type of the progenitor B cell tumor.

Original languageEnglish (US)
Pages (from-to)1253-1264
Number of pages12
JournalEuropean Journal of Immunology
Issue number4
StatePublished - 1999
Externally publishedYes


  • B lymphocyte
  • Clonal expansion
  • Ig gene
  • Somatic hypermuation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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