The transforming gene product of the t(2;5) translocation of anaplastic large cell lymphoma transactivates the HIV-LTR in CD4+ T-cells (Meeting abstract).

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

The transforming gene product of the t(2;5) translocation of anaplastic large cell lymphoma transactivates the HIV-LTR in CD4+ T-cells (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 38:A948 1997. Unique Identifier : AIDSLINE MED/97622089
Doseeva V; Butscher W; Wellmann A; Stetler-Stevenson M; Gardner K; Laboratory of Pathology, National Cancer Institute, National; Institutes of Health, Bethesda, MD

Abstract: Anaplastic large cell lymphomas (Ki-1 Lymphoma) are a subclass of human malignant lymphomas with a highly characteristic morphology. These tumors have also been found to occur as an uncommon subtype of AIDS associated lymphomas. Anaplastic large cell lymphoma is associated with a chromosomal translocation [t(2;5)(p23;q35)] that produces a chimeric fusion between B23/Nucleophosmin (NPM) and the catalytic domain of the anaplastic lymphoma kinase (ALK), a receptor protein tyrosine kinase (RPTK) distantly related to the insulin receptor tyrosine kinase family, but distinct from the nonreceptor tyrosine kinases active during receptor mediated T-cell activation. In addition to the potent transforming activity of NPM-ALK in several cell lines, we have found this fusion protein to induce potent transactivation of the HIV long terminal repeat (HIV-LTR). In order to elucidate the signal transduction pathways important in NPM-ALK dependent activation of HIV transcription, Jurkat human T-cells lines were transiently and stably transfected with cDNA encoding NPM-ALK. An analysis of an array of HIV-LTR reporter plasmids encoding various mutations, deletions, and isolated enhancers identifies the tandem repeated HIV-kB enhancer sites as the major targets of NPM-ALK downstream signaling in Jurkat T-cells. The transcriptional up regulation of both the HIV-LTR and the individual kB sites is dose dependent and requires a functional Ras for full activity. Analysis of nuclear and cytosolic extracts derived from NPM-ALK transformed Jurkat cells shows corresponding up regulation of kB specific DNA binding activity. These in vitro findings indicate that NPM-ALK can be a potent activator of HIV transcription and suggests a possible dual role for this gene in HIV pathogenesis and tumor progression in patients with AIDS associated anaplastic large cell lymphoma.

Keywords: *Chromosomes, Human, Pair 2 *Chromosomes, Human, Pair 5 *CD4-Positive T-Lymphocytes/METABOLISM *HIV Long Terminal Repeat *Lymphoma, AIDS-Related/GENETICS *Lymphoma, Large-Cell/GENETICS *Trans-Activation (Genetics) *Translocation (Genetics)
971230
M97C1603

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1997. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1997. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .