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Blood, Vol. 93 No. 5 (March 1), 1999:
pp. 1482-1486
RAPID COMMUNICATION
Detection of Kaposi's Sarcoma Herpesvirus DNA Sequences in Multiple
Myeloma Bone Marrow Stromal Cells
Dharminder Chauhan,
Ajit Bharti,
Noopur Raje,
Eric Gustafson,
Geraldine S. Pinkus,
Jack L. Pinkus,
Gerrard Teoh,
Teru Hideshima,
Steve P. Treon,
Joyce D. Fingeroth, and
Kenneth C. Anderson
From the Department of Adult Oncology, Dana-Farber Cancer Institute
and the Department of Medicine, Harvard Medical School; the Department
of Pathology, Brigham and Womens Hospital, and the Department of
Pathology, Harvard Medical School, Boston, MA.
Whether Kaposi's sarcoma herpesvirus (KSHV) is associated with
multiple myeloma (MM) remains controversial. We assayed for KSHV DNA
sequences in long-term bone marrow stromal cells (BMSCs) from 26 patients with MM and 4 normal donors. Polymerase chain reaction (PCR)
using primers which amplify a KSHV gene sequence to yield a 233-bp
fragment (KS330233 within open reading frame 26) was
negative in all cases. Aliquots of these PCR products were used as
templates in subsequent nested PCR, with primers that amplify a 186-bp
product internal to KS330233. BMSCs from 24 of 26 (92%)
patients with MM and 1 of 4 normal donors were KSHV PCR+.
DNA sequence analyses showed interpatient specific mutations (2 to 3 bp). Both Southern blot and sequence analyses confirmed the specificity
of PCR results. The presence of the KSHV gene sequences was further
confirmed by amplifying T 1.1 (open reading frame [ORF]
K7) and viral cyclin D (ORF 72), two other domains within the KSHV
genome. Immunohistochemical studies of KSHV PCR+ MM BMSCs
demonstrate expression of dendritic cell (DC) lineage markers (CD68,
CD83, and fascin). Serological studies for the presence of KSHV lytic
or latent antibodies were performed using sera from 53 MM patients, 12 normal donors, and 5 human immunodeficiency virus
(HIV)/KSHV+ patients. No lytic or latent antibodies were
present in sera from either MM patients or normal donors. Taken
together, these findings show that KSHV DNA sequences are detectable in
BMSCs from the majority of MM patients, but that serologic responses to
KSHV are not present. Ongoing studies are defining whether the lack of
antibody response is caused by the absence of ongoing infection, the
presence of a novel viral strain associated with MM, or underlying
immunodeficiency in these patients.

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