Increased level of stromal cell-derived factor-1 mRNA in peripheral blood mononuclear cells from children with AIDS-related lymphoma.
A common polymorphism in the 3' untranslated region of the stromal cell-derived factor 1 (also called pre-B-cell-stimulating factor) beta 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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HIV Clinical Interface Laboratory, Frederick Science Applications International Corporation-Frederick, National Cancer Institute at Frederick, Maryland 21702, USA.
O'Neill
D P
DP
Stewart
S K
SK
Yang
Q
Q
Kumagai
M
M
Boler
A M
AM
Adde
M A
MA
Zwerski
S L
SL
Wood
L V
LV
Venzon
D J
DJ
Magrath
I T
IT
D000293:Adolescent; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000235:genetics; D015497:HIV-1; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007223:Infant; D008221:Lymphoid Tissue / Q000378:metabolism; D016483:Lymphoma, AIDS-Related / Q000097:blood* / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000097:blood* / Q000235:genetics / Q000821:virology; D008297:Male; D012333:RNA, Messenger / Q000097:blood* / Q000378:metabolism; D019562:Viral Load
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D004279:DNA, Viral; D012333:RNA, Messenger