Translocation of immunoglobulin VH genes in Burkitt lymphoma.

Abstract

We have produced cell hybrids between mouse myeloma cells, which do not produce immunoglobulin chains, and Burkitt lymphoma cells (Daudi), which express surface IgM. Daudi Cells carry a reciprocal chromosome translocation between chromosomes 8 and 14, described as (8;14)(q24;q32). The hybrids were studied for the expression of human immunoglobulin chains and human isozyme markers, for the presence of human chromosomes, and for the presence of the human genes for heavy chain variable regions (VH) and mu and gamma chain constant (C) regions. The results indicate that the expressed mu chain gene is on normal chromosome 14 in Daudi cells. We have also determined that the chromosome 14 involved in the translocation (14q+) carries the gene for C mu and C gamma 1-4 and probably several genes for the variable region (V). Certain hybrids had lost both the chromosomes 14 but had retained the abnormal chromosome 8 (8q-) that carries the terminal end of the long arm of chromosome 14. These hybrids were studied for the presence of human VH, C mu,, and C gamma DNA sequences, and the results indicated that the hybrid cells with the 8q- chromosome contained VH genes that not C genes. Therefore, we conclude that, in the Daudi Burkitt lymphoma, the break in chromosome 14 occurred within the chromosome segment containing V region genes. As a result of the translocation some of these VH genes became associated with chromosome 8. It is possible that the expression of malignancy in Burkitt lymphoma is caused by immunoglobulin V region gene translocation resulting in activation of a gene on the long arm of human chromosome 8.

Bone morphogenetic proteins induce apoptosis in multiple myeloma cells by Smad-dependent repression of MYC

“…Similar translocations are common in Burkitt's lymphomas and plasmacytomas. Interestingly, the lymphoma cell line Daudi, harboring a t(8;14) translocation, 39 was resistant to BMP-induced apoptosis despite having proper BMP receptors and functional Smad signaling (TH, unpublished data).…”

Translocations involving 8q24 in Burkitt lymphoma and other malignant lymphomas: a historical review of cytogenetics in the light of todays knowledge

“…Variant translocations towards 2p and 22q were described in BL cell lines in 1979. 6,7 The molecular targets of these translocations were discovered to be MYC (at 8q24), 8,9 and genes coding for the immunoglobulin heavy chain (IGH at 14q32), 10 kappa light chain (IGK at 2p12) 11 and lambda light chain (IGL at 22q11). 12 All translocations juxtapose the MYC gene to one of the IG enhancers, which results in constitutive deregulation of MYC expression.…”

Activation of a translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus

“…From a cosmid library 19 of Manca DNA a clone, cU23 was isolated that hybridized both to v-myc and to pH18-C1-10, a plasmid containing the immunoglobulin heavy-chain C μ gene and sequences immediately 5' to it 20 . Southern blot analysis 21 of Manca DNA indicated that the linkage of c-myc and immunoglobulin heavy-chain gene sequences detected in cU23 had occurred in the human cells, and not upon cloning (data not shown).…”