Hakim, I., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Rechavi, G., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Brok-Simoni, F., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Grossman, Z., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Amariglio, N., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Mandel, M., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Ramot, B., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Ben-Bassat, I., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Katzir, N., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel
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.
Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia
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Hakim, I., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Rechavi, G., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Brok-Simoni, F., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Grossman, Z., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Amariglio, N., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Mandel, M., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Ramot, B., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Ben-Bassat, I., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel Katzir, N., Institute of Haematology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel
Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia
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.