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Increased Level of Stromal Cell-Derived Factor-1 mRNA in Peripheral Blood Mononuclear Cells from Children with AIDS-related Lymphoma¹

HIV Clinical Interface Laboratory, Frederick Science Applications International Corporation-Frederick, National Cancer Institute at Frederick, Frederick, Maryland 21702 [S. S., D. P. O., Q-e. Y.]; HIV and AIDS Malignancy Branch [S. K. S., M. K., A. M. B., S. L. Z., L. V. W.], Biostatistics and Data Management Section [D. J. V.], and Pediatric Oncology Branch [M. A. A., I. T. M.], Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892

A common polymorphism in the 3' untranslated region of the stromal cell-derived factor 1 (also called pre-B-cell-stimulating factor) ß gene transcript, termed SDF1–3'A, has been associated with an increased risk of non-Hodgkin’s lymphoma (NHL) in HIV-1-infected, but not in uninfected, individuals. Because the gene variation is located within the 3' untranslated region, the SDF1–3'A may influence the abundance of SDF-1 mRNA, possibly up-regulating the chemokine expression especially in the presence of HIV-1. In the current study, we investigated the levels of SDF-1 mRNA in peripheral blood mononuclear cells and HIV-1 viral load in 84 HIV-1-infected children (0.7 to 18 years of age; median, 5.8), including 12 children who developed NHL during their illnesses (AIDS-NHL group; 8 with SDF1–3'A, 4 with SDF1-wild-type). High level SDF-1 expression was observed in 15 of 34 children with SDF1–3'A as compared with 10 of 50 with wild type (P < 0.03). More notably, the children with AIDS-NHL had significantly elevated levels of SDF-1 mRNA in peripheral blood mononuclear cells, obtained at the time of presentation in 10 children and 8.5 to 19.4 months before (median, 15 months) in 7 children, as compared with the children in the non-NHL group (P < 0.00001). The amounts of cell-associated HIV-1 DNA and singly spliced HIV-1 mRNA were significantly greater in children with AIDS-NHL than those with non-NHL AIDS (P = 0.0052 and 0.011, respectively; stratified by antiretroviral treatment regimen), whereas their serum HIV-1 RNA levels were comparable. Overexpression of SDF-1 and aberrant HIV-1 expression in circulating lymphocytes appear to be linked to the development of AIDS-lymphoma. Additional studies are required to determine whether excessive SDF-1, together with virally encoded factors, is directly involved in the pathogenesis of AIDS-lymphoma.

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