Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
FACTORS IN THE DEVELOPMENT OF AIDS-RELATED LYMPHOMAS (MEETING ABSTRACT)
Fifteenth Symposium of the International Association for Comparative Research on Leukemia and Related Diseases. October 6-11, 1991, Padova/Venice, Italy, p. 9, 1991.. Unique Identifier : AIDSLINE ICDB/92682367 Broder S; NCI, Bethesda, MD
Abstract:
The association between AIDS and a spectrum of malignancies relates to chronic, profound defects in both cellular and humoral mechanisms of immune surveillance. Furthermore, viruses in addition to HIV may act directly or indirectly as 'cofactors' to induce malignant transformation. As AIDS patients (pts) live longer in response to increasingly effective antiretroviral therapies, the incidence of AIDS-related malignancies will continue to rise. In particular, a remarkable occurrence of high-grade B-cell non-Hodgkin's lymphomas (NHL) has emerged as a major sequela of HIV infection, especially in pts who survive other consequences of AIDS for a protracted period of time. AIDS-NHL display aggressive clinical behavior and unusual patterns of organ involvement, including the gastrointestinal tract, bone marrow and CNS. On the genomic level, c-myc is often translocated to the immunoglobulin gene locus, most commonly to the heavy chain gene (t[8;14][q24;q32]), with resultant transcriptional activation, deregulation and overexpression of the c-myc oncogene. In addition, Epstein-Barr virus (EBV) DNA is detectable in some malignant B cells and, in some cases, precedes full-blown NHL development, implicating EBV in the pathogenesis of some AIDS-NHL. Profound cellular immunodeficiency plays a central role in lymphomagenesis, as demonstrated by the striking relationship between the depletion of CD4 lymphocytes and development of NHL, particularly when the CD4 count falls below 50/mm3. The HIV-infected monocyte acts as both a cellular reservoir for infective viral particles and as a site for the production of B-cell-stimulating lymphokines, in particular interleukin-6 and, thus, may be important to abnormalities of growth and eventual malignant transformation in NHL. Definition of the roles of monocytes and B-stimulating and potential T-suppressing lymphokines (for example, interleukin-10) in the genesis and clonal expansion of transformed B cells may lead to identification of lymphokine inhibitors for eventual clinical application. The potential contributions of specific viruses or antiviral therapies to the pathogenesis of AIDS-NHL by inducing genetic instability and DNA damage (DNA breaks, aberrant gene rearrangements) or altering host cell or viral genome repair are future targets of investigation. The definition of multiple factors on a molecular level that confer heightened susceptibility to malignant transformation in the AIDS pt is aimed at the development of both therapeutic and preventive strategies. This line of research has implications not only in AIDS but to the entire spectrum of lymphomas.
Keywords: Bone Marrow Cell Transformation, Neoplastic/GENETICS Central Nervous System CD4-Positive T-Lymphocytes Disease Reservoirs DNA Damage/GENETICS DNA Repair/GENETICS DNA, Viral/ANALYSIS Gastrointestinal System Gene Expression Genes, Immunoglobulin/GENETICS Genome, Viral Herpesvirus 4, Human/GENETICS Human Interleukin-10 Interleukin-6/METABOLISM Leukocyte Count Lymphoma, AIDS-Related/*GENETICS/METABOLISM Monocytes/MICROBIOLOGY Proto-Oncogene Proteins c-myc/GENETICS Transcription, Genetic Translocation (Genetics) ABSTRACT
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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.
