Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia

Itzchak Hakim, Gideon Rechavi*, Frida Brok‐Simoni, Zehava Grossman, Ninetta Amariglio, Mathilda Mandel, Bracha Ramot, Isaac Ben‐Bassat, Nurit Katzir

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 JH 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 JH 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.

Original languageEnglish
Pages (from-to)436-442
Number of pages7
JournalBritish Journal of Haematology
Volume84
Issue number3
DOIs
StatePublished - Jul 1993

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