Detection of Kaposi's sarcoma herpesvirus DNA sequences in multiple myeloma bone marrow stromal cells

Whether Kaposi's sarcoma herpesvirus (KSHV) is associated with multiple mye loma (MM) remains controversial. We assayed for KSHV DNA sequences in long- term bone marrow stromal cells (BMSCs) from 26 patients with MM and 4 norma l donors. Polymerase chain reaction (PCR) using primers which amplify a KSH V gene sequence to yield a 233-bp fragment (KS330(233) within open reading frame 26) was negative in all cases. Aliquots of these PGR products were us ed as templates in subsequent nested PCR, with primers that amplify a 186-b p product internal to KS330(233). BMSCs from 24 of 26 (92%) patients with M M and 1 of 4 normal donors were KSHV PCR+. DNA sequence analyses showed int erpatient specific mutations (2 to 3 bp). Both Southern blot and sequence a nalyses confirmed the specificity of PCR results. The presence of the KSHV gene sequences was further confirmed by amplifying T 1.1 (open reading fram e [ORF] K7) and viral cyclin D (ORF 72), two other domains within the KSHV genome. Immunohistochemical studies of KSHV PCR+ MM BMSCs demonstrate expre ssion of dendritic cell (DC) lineage markers (CD68, CD83, and fascin). Sero logical studies for the presence of KSHV lytic or latent antibodies were pe rformed using sera from 53 MM patients, 12 normal donors, and 5 human immun odeficiency virus (HIV)/KSHV+ patients. No lytic or latent antibodies were present in sera from either MM patients or normal donors. Taken together, t hese findings show that KSHV DNA sequences are detectable in BMSCs from the majority of MM patients, but that serologic responses to KSHV are not pres ent. Ongoing studies are defining whether the lack of antibody response is caused by the absence of ongoing infection, the presence of a novel viral s train associated with MM, or underlying immunodeficiency in these patients. (C) 1999 by The American Society of Hematology.