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Novel concepts in the pathogenesis of HIV‐lymphoma
Author(s) -
Zenger E.
Publication year - 2004
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/j.1476-5810.2004.0045o.x
Subject(s) - pathogenesis , lymphoma , immunology , biology , carcinogenesis , disease , phenotype , antigen , macrophage , chemokine , cancer research , cancer , medicine , pathology , gene , inflammation , in vitro , genetics
Lymphoma remains a rapidly fatal consequence of HIV infection in developed countries despite the widespread use of highly active antiretroviral therapy. HIV‐associated lymphomas are predominantly of B‐cell origin, appearing to be outgrowths of antigen‐driven B‐cells with significant growth control influence provided by abnormal T‐cell and antigen‐presenting cells processes. Findings of clonal HIV integration within macrophages in a subset of these lymphomas provided evidence for abnormalities outside the B‐cell compartment playing roles in this disease. From this and other observations, the “sequential neoplasia” model, wherein a clonal macrophage would drive early stages of tumorigenesis, with sequential evolution of an independent tumor (1,2), emerged. To investigate this, we developed a pathogenesis‐based animal model of lymphoma wherein macrophages play an essential role in the lymphomagenesis process (3). Extensive phenotypic and genotypic analysis of human and murine tumors and associated macrophages revealed significant abnormalities providing compelling evidence that may explain the underlieing abnormalities and driving forces in AIDS‐associated lymphomas. Altered expression of specific cytokines, chemokines, and transcriptional activators have been detected that likely play a central role in the pathogenesis of this disease and possibly lymphoma in general.