A 14;18 and an 8;14 chromosome translocation in a cell line derived from an acute B-cell leukemia.

Abstract

We have established a cell line, which we named 380, from a young male with acute lymphoblastic leukemia (FAB type L2). Karyologic analysis of this cell line indicates that it carries an 8;14 and a 14;18 chromosome translocation, which are characteristic of Burkitt lymphoma and of follicular lymphoma, respectively. This cell line is Epstein-Barr virus antigen-negative, reacts with monoclonal antibodies specific for B cells, and contains rearranged immunoglobulin heavy and light chain genes, but does not express human immunoglobulins. In this cell line, both mu heavy chain constant (C mu) loci are rearranged within the joining (JH) DNA segment. One of the JH segments on one of the 14q+ chromosomes is rearranged with a segment of chromosome 8, where the c-myc oncogene resides, while the other is rearranged with a segment of chromosome 18 where a putative oncogene, which we have called bcl-2, is located. The c-myc oncogene, which is translocated to one of the 14q+ chromosomes, is in its germ-line configuration more than 14 kilobases away from both the JH segment and the heavy chain enhancer that is located between the JH and mu switch region. Based on these findings, we propose a model of some aspects of B-cell oncogenesis according to which B-cell neoplasms carrying translocations involving the heavy chain loci on both human chromosomes 14 are the result of a multiple step process.

Intragenomic conflict and cancer

“…For example, the mitochondrial elongation factor Tu, necessary for protein synthesis in mitochondria, has been found to be over-expressed in tumor cells (94). The Bcl-2 proto-oncogene was originally discovered as a chromosomal translocation leading to the up-regulation of the gene in B cell lymphoma (95). It has since been determined that Bcl-2 is over-expressed in different types of cancer cells, including lymphoma, breast and prostate (96)(97)(98).…”

Inducible resistance to Fas-mediated apoptosis in B cells

“…These studies together strongly suggest that FLIP is involved in bringing about sIg-induced resistance to Fas-mediated apoptosis because the two criteria discussed above were met, as described earlier for Bcl-xL: FLIP expression was upregulated coordinately with induction of Fas-resistance by anti-Ig, and isolated FLIP overexpression diminished B cell susceptibility to Fas signaling for cell death. (In these studies a number of other known anti-apoptotic genes screened as outlined above failed to meet the criterion of expression coincident with induction of Fas-resistance, including A1, A20, BAG-1, Bcl-2, IAP-1, IAP-2, Ich-1S, IEX-1L and survivin, references [82][83][84][85][86][87][88][89][90].…”

Bcl-2 overexpression blocks caspase activation and downstream apoptotic events instigated by photodynamic therapy

“…Bcl-2 was discovered as an overexpressed protein in human B-cell lymphomas arising as a result of a t(14;18) chromosomal translocation (Pegoraro et al, 1984;Tsujimoto et al, 1985). The overexpression of Bcl-2 has been shown to protect different cell types against apoptosis induced by such diverse stimuli as viral infection, hypoxia, ionizing radiation or chemotherapeutic agents (Shimizu et al, 1995;Gajewski and Thompson, 1996;Ibrado et al, 1996Ibrado et al, , 1997Reed, 1996).…”