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M94A2984.TXT
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1994-10-25
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Document 2984
DOCN M94A2984
TI Pathogenesis of AIDS associated large cell lymphoma.
DT 9412
AU Tsuzuki A; Herndier B; Marsh J; Ng V; Nolan T; Shiramizu B; McGrath M;
University of California, San Francisco.
SO Int Conf AIDS. 1994 Aug 7-12;10(1):18 (abstract no. 045B). Unique
Identifier : AIDSLINE ICA10/94369591
AB OBJECTIVE: The pathogenesis of HIV associated Burkitt's lymphoma
probably revolves around dysregulation of the c-myc proto-oncogene. For
other AIDS associated lymphomas, particularly the large cell lymphomas
(LCL), the pathogenesis is unclear, particularly when some
pre-lymphomatous states or even frank lymphomas are polyclonal in nature
and can in some cases lack demonstrable EBV. This study examines the
phenotype of such lymphomas and viral and cytokine expression with the
hopes of unravelling the key events in the early stages of
lymphomagenesis in HIV disease. METHODS: A consecutive series of 15
large cell lymphomas and malignant effusions were examined by the
following techniques: 1) morphology; 2) 3-color cytofluorometry; 3)
frozen section immunohistochemistry; 4) reverse transcriptase PCR
followed by Southern blotting (IL-6, IL-6R, IL-10); 5) PCR, Southern
blotting and in situ hybridization with an EBV EBER probe. RESULTS AND
CONCLUSIONS: Twelve of 15 LCL expressed IL-6R RNA and 11/15 IL-10 RNA,
indicating the possibility of Il-6/IL-6R and/or IL-10/IL-10R
interactions being important in lymphoma growth. Growth studies with
cell lines established from malignant effusions indicate both paracrine
IL-6/IL-6R and autocrine (IL-6/IL-6R) growth analogous to what has been
observed with human multiple myeloma. Six of 7 studied LCL were composed
of CD5 positive B cells, the B cell thought to be important in
autoimmunity and known to respond to IL-10 as an autocrine growth
factor. Neutralizing antibodies to both IL-6 and IL-10 inhibited
proliferations of two newly established AIDS LCL cell lines, suggesting
that both IL-6 and IL-10 may play important roles in AIDS
lymphomagenesis. Our data (7/15 cases) does not support a consistent
role for EBV.
DE Antigens, CD/ANALYSIS Blotting, Southern Flow Cytometry Human HIV
Infections/*COMPLICATIONS Immunohistochemistry In Situ Hybridization
Interleukins/ANALYSIS Lymphoma, AIDS-Related/CHEMISTRY/*GENETICS
Lymphoma, Large-Cell/CHEMISTRY/*GENETICS Polymerase Chain Reaction
MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).