Detection of Human Herpesvirus-8 DNA in Bone Marrow Biopsies From Patients With Multiple Myeloma and Waldenström's Macroglobulinemia

To the Editor:

Said et al1 recently showed that human herpesvirus-8 (HHV-8) DNA could be amplified from bone marrow biopsies of patients with multiple myeloma (MM). These data reinforce their initial findings in cultured bone marrow cells and rule out the possibility that detection of HHV-8 in cultivated dendritic cells may be artifactual. However, the biology of HHV-8 in MM remains controversial because serologic studies are negative,3,4 although antibodies are usually detectable in other HHV-8–associated disease's such as Kaposi's sarcoma or cavity-based lymphomas. We obtained data in 10 patients with myeloma that support the findings of Berenson's group. In addition, we studied 10 patients with Waldenström's macroglobulinemia (WM).

Polymerase chain reaction (PCR) amplification was made with KS330₂₃₃-specific primers on DNA extracted from paraffin-embedded bone marrow sections. We obtained fragments of the expected size that hybridized with an internal probe in 5 out of 10 bone marrow biopsies from patients with MM (Fig1). Furthermore, there were different point mutations in the two PCR products that were sequenced as compared with the original sequence. These data make PCR artifacts unlikely.

No amplification was noted with DNA from 10 normal bone marrow samples and 9 out of 10 bone marrow biopsies from patients with non-Hodgkin's lymphomas (the one positive case presented with follicular lymphoma). In vitro long-term bone marrow cultures from 3 MM patients were also studied; 2 of 3 were positive for HHV-8 sequences. HHV-8 PCR performed on bone marrow biopsy from the negative sample was also negative. Interestingly, no antibodies to lytic HHV-8 antigens were detectable by immunofluorescence in the sera of MM patients or controls.

Detection of HHV-8 DNA on bone marrow biopsies may be less sensitive than other techniques; nevertheless, it shows that HHV-8 infection exists in vivo and offers the opportunity to determine the onset and fate of HHV-8 infection in MM patients.

These results prompted us to similarily study bone marrow biopsies from patients with WM. Amplification of HHV-8 sequences was obtained in 6 out of 10 samples studied (fig 1). Again no antibodies to HHV-8 were detected in WM patients' sera. Interestingly, the pathogenesis of WM involves interleukin-6,5 a cytokine with a viral HHV-8 homolog that may play a key role in the development of MM as postulated by Said et al.1