CHROMOSOMAL TRANSLOCATIONS REVEAL NOVEL PROTO-ONCOGENES (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

CHROMOSOMAL TRANSLOCATIONS REVEAL NOVEL PROTO-ONCOGENES (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 33:A603-4 1992. Unique Identifier : AIDSLINE ICDB/92687947
Korsmeyer SJ; Dept. of Medicine, Washington Univ. Sch. of Medicine, St. Louis,; MO 63110

Abstract: Bcl-2 is a 25-kD integral mitochondrial membrane protein that blocks programmed cell death without promoting cell division. The t(14;18) chromosomal breakpoint found in follicular B-cell lymphoma juxtaposes Bcl-2 with the Ig heavy chain gene, resulting in marked overproduction of Bcl-2. Transgenic mice bearing a Bcl-2-Ig minigene that recapitulates the t(14;18) initially display a polyclonal expansion of resting B cells with a prolonged life-span. Over time these mice develop monoclonal, high-grade lymphomas which often possess a c-myc translocation. Extended cell survival appears to be a key event which favors the acquisition of secondary genetic events. Bcl-2-Ig mice which overproduced Bcl-2 provide an in vivo model to assess the role of Bcl-2 in immune responsiveness. Markedly protracted secondary immune responses by these transgenics resulted from long-term persistence of antibody-secreting plasma cells as well as an extended lifetime for resting memory B cells. Bcl-2 inhibits multiple forms of apoptosis but not negative selection within thymocytes. Regulators of cell death constitutes a new class of proto-oncogenes. Bcl-2 establishes one subset of this category: antidotes to cell death that function in an autosomal dominant fashion. A second subset is predicted: genes that would represent the actual effectors of apoptosis, manifest by an autosomal recessive mechanism. The most frequent interchromosomal translocations within T-cell neoplasms involve their antigen receptor genes. Analysis of transcripts from other participating chromosomes has identified new transcription factor genes. Studies involving cloned breakpoints of the t(11;14)(p15;q11) in a CD3-negative T-cell acute lymphoblastic leukemia cell line (RPMI 8402) are discussed. (16 Refs)

Keywords: Antigens, Differentiation, T-Lymphocyte/ANALYSIS B-Lymphocytes/PHYSIOLOGY Cell Death CD4-CD8 Ratio Genes, Homeobox Leukemia, T-Cell/GENETICS Lymphoma/GENETICS Mice Mice, Transgenic Mitochondria/PHYSIOLOGY Oncogene Proteins/GENETICS Proto-Oncogene Proteins/GENETICS/IMMUNOLOGY Receptors, Antigen, T-Cell/ANALYSIS T-Lymphocytes/PHYSIOLOGY Thymus Gland/CYTOLOGY Translocation (Genetics)/*GENETICS ABSTRACT
921230
M92C5368

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