Premium
Bcl‐2 rearrangements with breakpoints in both vcr and mbr in non‐Hodgkin’s lymphomas and chronic lymphocytic leukaemia
Author(s) -
Merup Mats,
Spasokoukotskaja Tatjana,
Einhorn Stefan,
Edvard Smith C. I.,
Gahrton Gösta,
Juliusson Gunnar
Publication year - 1996
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 - 10.1046/j.1365-2141.1996.00388.x
Subject(s) - breakpoint , gene rearrangement , chronic lymphocytic leukemia , immunoglobulin heavy chain , chromosomal translocation , lymphoma , biology , follicular lymphoma , gene , immunoglobulin light chain , immunoglobulin gene , cancer research , microbiology and biotechnology , antibody , leukemia , genetics , immunology
The bcl‐2 gene is rearranged in most cases of follicular lymphoma and the breakpoint clusters into two specific regions: mbr and mcr. Rearrangements to immunoglobulin heavy chain genes (IgH) result in a deregulation of the gene and increased transcription of mRNA for the bcl‐2 protein. In chronic lymphocytic leukaemia (CLL) expression of bcl‐2 protein is increased but rearrangement of the gene can be found only in a minority of cases; commonly a variant translocation with a breakpoint region located 5′ of the bcl‐2 gene (vcr) with preferential rearrangement to immunoglobulin light chain genes. We have analysed breakpoints in mbr and vcr in malignant cells from 96 patients with B‐CLL, 45 with hairy cell leukaemia (HCL) and 41 with high‐ and low‐grade non‐Hodgkin’s lymphomas (NHL). Vcr rearrangements were observed in nine patients (12%) with B‐CLL. Four patients had co‐migration of rearranged bcl‐2 bands to kappa genes and two patients to IgH. Cytogenetic abnormalities involving 18q21, the site of the bcl‐2 gene, was found in two cases only. In several cases with bcl‐2 gene rearrangement chromosomal aberrations not including 18q21 were observed. In six patients (two B‐CLL, one follicular lymphoma, one immunocytoma and two high‐grade lymphomas), breakpoints in both vcr and mbr were found. In HCL a rearrangement in the vcr region was found in one case. Bcl‐2 protein immunostaining of B‐CLL showed intense bcl‐2 expression in all cases and no correlation was found between gene rearrangement and protein expression. Our study confirms that breakpoints in the bcl‐2 gene commonly cluster to the vcr region in B‐CLL, but in most cases over‐expression of bcl‐2 protein has to be explained by other mechanisms than bcl‐2 gene rearrangement. We also report that simultaneous breakpoints in mbr and vcr is a recurrent phenomenon in B‐CLL and in other high‐ and low‐grade non‐Hodgkin’s lymphomas.