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The B cell antigen receptor in atypical chronic lymphocytic leukemia with t(14;19)(q32;q13) demonstrates remarkable stereotypy
Author(s) -
Schweighofer Carmen D.,
Huh Yang O.,
Luthra Rajyalakshmi,
Sargent Rachel L.,
Ketterling Rhett P.,
Knudson Ryan A.,
Barron Lynn L.,
Medeiros L. Jeffrey,
Keating Michael J.,
Abruzzo Lynne V.
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25605
Subject(s) - ighv@ , biology , chronic lymphocytic leukemia , immunoglobulin heavy chain , immunoglobulin light chain , complementarity determining region , antigen , chromosomal translocation , gene rearrangement , antibody , breakpoint cluster region , gene , germline , surface immunoglobulin , t cell receptor , leukemia , b cell , genetics , t cell , immune system
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.