The B cell antigen receptor in atypical chronic lymphocytic leukemia with t(14;19)(q32;q13) demonstrates remarkable stereotypy

Carmen D. Schweighofer, Yang O. Huh, Rajyalakshmi Luthra, Rachel L. Sargent, Rhett P. Ketterling, Ryan A. Knudson, Lynn L. Barron, L. Jeffrey Medeiros, Michael J. Keating, Lynne V. Abruzzo

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The t(14;19)(q32;q13) is a recurrent chromosomal translocation reported in a variety of B-cell leukemias and lymphomas, including chronic lymphocytic leukemia (CLL). CLL cases associated with t(14;19) often have atypical morphologic and immunophenotypic features and unmutated immunoglobulin heavy chain (IGH) variable region (V) genes, associated with an aggressive clinical course. We analyzed IGHV somatic mutation status and gene use in 11 patients with t(14;19)-positive CLL. All cases were unmutated, and the IGHV genes in 10 cases showed minimal deviation from germline sequences. In 7 of 11 patients, we found homologous heavy chain rearrangements using IGHV4-39; light chain analysis revealed identical IGKV1-39 use. Corresponding V-(D)-J sequences demonstrated remarkable stereotypy of the immunoglobulin heavy and kappa light chain complementarity determining region 3 (H/K CDR3) genes. These findings raise the possibility that specific antigen drive is involved in the clonal development and/or selection of t(14;19)(q32;q13)-positive CLL cells. Our findings support the hypothesis that stimulatory signals through specific antigen receptors may promote the expansion of either CLL precursor cells or CLL clones that harbor distinct chromosomal abnormalities.

Original languageEnglish (US)
Pages (from-to)2759-2764
Number of pages6
JournalInternational Journal of Cancer
Volume128
Issue number11
DOIs
StatePublished - Jun 1 2011

Keywords

  • B cell receptor
  • CLL
  • atypical
  • stereotypy
  • t(14;19)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Schweighofer, C. D., Huh, Y. O., Luthra, R., Sargent, R. L., Ketterling, R. P., Knudson, R. A., Barron, L. L., Medeiros, L. J., Keating, M. J., & Abruzzo, L. V. (2011). The B cell antigen receptor in atypical chronic lymphocytic leukemia with t(14;19)(q32;q13) demonstrates remarkable stereotypy. International Journal of Cancer, 128(11), 2759-2764. https://doi.org/10.1002/ijc.25605