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.