AEGiS-07CROI: HIV implicated in the cis-activation of c-fes in a subset of HIV-associated lymphomas.

7th Conference on Retroviruses and Opportunistic Infections

San Francisco, CA - January 30 -February 4, 2000

HIV IMPLICATED IN THE cis-ACTIVATION OF c-fes IN A SUBSET OF HIV-ASSOCIATED LYMPHOMAS.

Conf Retroviruses Opportunistic Infect 2000 Jan 30-Feb 2; 7:76 (abstract no. 6)

K. Mack¹, R. Wei², B. Herndier², B. Shiramizu², N. Abbey², R. Gascon², A. Elbaggari², M. Hurt², T. Earnst³, And M. Mcgrath²
¹SLIL Biomed. Corp., Menlo Park, CA; ²Univ. of California, San Francisco Gen. Hosp., CA; and ³Harvard Med. Sch., Boston, MA

Clonal HIV insertions upstream of the proto-oncogene c-fes were identified in a subset of AIDS-associated high-grade non-Hodgkin's lymphomas. These lymphomas included large cell lymphomas interspersed with prominent macrophages and a T-cell lymphoma. In a representative case of these neoplasias, tumor associated macrophages were characterized and found to co-express the proto-oncogene c-fes and HIV p24. The c-fes gene product, p93-c-fes was found in an activated, phosphorylated state in macrophages isolated from this tumor tissue. An HIV promoter insertion model characterized 3'LTR mediated cis-activated expression through the c-fes upstream genomic region in the human Jurkat T-cell line, K562 myeloid progenitor cell line, and primary cultured human macrophages. The cotransfection of a c-fes cDNA enhanced 3'LTR cis-activation through the c-fes upstream genomic region indicating the possible presence of a positive feedback mechanism that potentiates gene dysregulation. This study presents further evidence for tumor-associated retroviral-mediated insertional mutagenesis at a specific genomic locus in humans that may play a direct role in lymphomagenesis.

Keywords: AEGIS, Proto-Oncogenes, Lymphoma, HIV, Promoter Regions (Genetics), Macrophages, DNA Primers, DNA, Tumor Cells, Cultured, HIV-1, HIV Long Terminal Repeat, Commonwealth of Independent States, Human, genetics, AIDS

2000-01-30
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Copyright © 2000 - Foundation for Retrovirology and Human Health (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed from National Library of Medicine.