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Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia
Author(s) -
Hakim Itzchak,
Rechavi Gideon,
BrokSimoni Frida,
Grossman Zehava,
Amariglio Ninetta,
Mandel Mathilda,
Ramot Bracha,
BenBassat Isaac,
Katzir Nurit
Publication year - 1993
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1993.tb03098.x
Subject(s) - biology , southern blot , immunoglobulin heavy chain , gene rearrangement , germline , immunoglobulin light chain , gene , antibody , immunoglobulin gene , hindiii , genetics , microbiology and biotechnology , allele , restriction site , restriction enzyme
Summary. Chronic lymphocytic leukaemia (CLL) is known to be a stable monoclonal neoplasm. In contrast to early studies demonstrating no more than two hybridizing immunoglobulin heavy chain bands corresponding to the two expected alleles, we have demonstrated an unexpected multiband pattern when the HindIII‐digested DNA samples from 38 CLL patients were analysed by Southern blot hybridization using J H and Cμ gene probes. In order to characterize the genetic basis for the multiband pattern, we molecularly cloned the immunoglobulin heavy chain genes of one of the patients whose leukaemic DNA sample demonstrated three hybridizing J H bands and a loss of the germline band. The cloned rearranged immunoglobulin genes could be divided, based on the restriction mapping and the hybridization with the various probes, into two basic patterns representing two alleles. In one of the cloned rearranged immunoglobulin genes a secondary rearrangement occurred that resulted in the addition of 300 base‐pair long sequence into the switch region, and the creation of a HindIII restriction site. The results of the study suggest that clonal evolution occurs in some CLL, and that many of these neoplasms are indeed oligoclonal due to the accumulation of secondary genetic changes.