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

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.

journal_name

Int J Cancer

authors

Schweighofer CD,Huh YO,Luthra R,Sargent RL,Ketterling RP,Knudson RA,Barron LL,Medeiros LJ,Keating MJ,Abruzzo LV

doi

10.1002/ijc.25605

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

2759-64

issue

11

eissn

0020-7136

issn

1097-0215

journal_volume

128

pub_type

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