Molecular analysis of light-chain switch and acute lymphoblastic leukemia transformation in two follicular lymphomas: Implications for lymphomagenesis

Carol Kobrin, Soung Chul Cha, Hong Qin, Mark Raffeld, Falko Fend, Leticia Quintanilla-Martinez, Sheldon Grove, Elaine S. Jaffe, Larry W. Kwak

Research output: Contribution to journalArticle

Abstract

We observed novel transformations of follicular lymphoma (FL), first, a switch in immunoglobulin (Ig) light chain, and second, transformation of FL to acute lymphoblastic leukemia (ALL). Each set of tumors shared a common clonal origin, as demonstrated by expression of identical, unique CDR IIIH sequences, shared somatic mutations in JH, and identical bcl-2 translocation breakpoints of microdissected ALL cells. Molecular analysis of lambda V-gene expression demonstrated lambda-bearing cells in the original kappa tumor, while expansion of the lambda subclone at relapse occurred after active immunotherapy targeting the Ig receptor. These exceptional cases are compatible with a more contemporary model of lymphomagenesis in which critical events originate from genetic mechanisms which normally occur in germinal center (GC) B cells and challenge the current paradigm of parallel generation of subclones from an early, pre-GC precursor. It is also possible that the outgrowth of these variants was a consequence of immunoselection.

Original languageEnglish (US)
Pages (from-to)1523-1534
Number of pages12
JournalLeukemia and Lymphoma
Volume47
Issue number8
DOIs
StatePublished - Aug 1 2006

Keywords

  • Idiotype vaccine
  • Immune selection
  • Immunoglobulin (Ig) receptor revision

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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