Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
ONCOGENES AND TUMOR-SUPPRESSOR GENES IN B-CELL LYMPHOMA PATHOGENESIS (MEETING ABSTRACT)
Fifteenth Symposium of the International Association for Comparative Research on Leukemia and Related Diseases. October 6-11, 1991, Padova/Venice, Italy, p. 13, 1991.. Unique Identifier : AIDSLINE ICDB/92682369 Dalla-Favera R; Dept. of Pathology, Coll. of Physicians and Surgeons, Columbia; Univ., New York, NY 10032
Abstract:
A group of B-cell malignancies including Burkitt's lymphoma (BL), L3-type acute lymphoblastic leukemia (ALL) and AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL) are associated with specific chromosomal translocations involving the c-myc and immunoglobulin loci. The consequences of these abnormal recombinations are (1) the juxtaposition of the c-myc gene to immunoglobulin regulatory domains and (2) structural lesions including truncations and mutations of the 5' regulatory region of translocated c-myc alleles. Both these events are thought to be necessary to cause deregulation of c-myc gene expression. Constitutively expressed c-myc alleles have been shown to transform EBV-immortalized human B lymphoblasts in vitro and to cause B-cell tumors in transgenic mice. Deregulated c-myc expression leads to changes in the regulation of genes that are regulated by c-myc. It has been found that the gene coding for the alpha(L) chain of LFA-1 (alpha[L]/beta 2) integrin receptor is specifically modulated by c-myc by a post-transcriptional mechanism in B-lymphoblastoid cells transfected with c-myc oncogenes as well as in Burkitt's lymphoma cells which carry activated c-myc oncogenes. Since LFA-1 is involved in B-cell adhesion to cytotoxic T cells and NK cells, as well as to vascular endothelia, these results imply novel functions for the c-myc gene both in controlling normal B-cell development and in determining the ability of tumor cells to escape immunosurveillance and metastasize. Consistent with this notion, transformation by c-myc oncogenes has been found associated with resistance to autologous T-cell-mediated cytotoxicity in vitro. Multiple genetic alterations, in addition to c-myc oncogene activation, are likely to be required for lymphomagenesis. While EBV infection is likely to play a role in BL and AIDS-NHL, recent evidence indicates that loss/mutation/inactivation of p53 and RB 'tumor suppressor' genes may also be involved. In particular, loss/inactivation of the p53 gene is associated at high frequency (50-70%) with all types of neoplasms carrying activated c-myc oncogenes including L3-type ALL, whereas it is very rarely found in other types of ALL and NHL. These results suggest that specific interactions may exist between c-myc and p53 in B lymphomagenesis.
Keywords: Burkitt's Lymphoma/*GENETICS Cell Transformation, Neoplastic/GENETICS Gene Expression Gene Expression Regulation Genes, Immunoglobulin/*GENETICS Genes, Retinoblastoma/GENETICS Genes, Suppressor/*GENETICS Herpesvirus 4, Human/GENETICS Human Integrins/GENETICS Leukemia, Lymphocytic, Acute/*GENETICS Lymphocyte Function-Associated Antigen-1/GENETICS Lymphoma, AIDS-Related/*GENETICS Protein p53/GENETICS Proto-Oncogene Proteins c-myc/*GENETICS T-Lymphocytes, Cytotoxic Transcription, Genetic Translocation (Genetics)/*GENETICS ABSTRACT 920830
M9281111
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
