Initiation and maintenance of multiple myeloma

Area of Science:

• Hematology
• Oncology
• Virology

Background:

• Human herpesvirus-8 (HHV-8), or Kaposi's sarcoma (KS)-associated herpesvirus, has been detected in nonmalignant bone marrow dendritic cells and peripheral blood of multiple myeloma patients.
• HHV-8 presence in peripheral blood may correlate with disease progression, as it's absent in earlier stages.
• The virus is not found in family members or sexual partners of myeloma patients, indicating a specific association.

Purpose of the Study:

• To investigate the presence and potential role of HHV-8 in the pathogenesis of multiple myeloma.
• To analyze genetic alterations in myeloma cells, including chromosome translocations and mutations.
• To explore the role of angiogenesis in multiple myeloma progression and its potential modulation.

Main Methods:

• Detection of HHV-8 in peripheral blood and bone marrow dendritic cells of multiple myeloma patients.
• Sequencing of HHV-8 open-reading frames (ORFs) to identify variations.
• Analysis of myeloma cell lines for chromosome translocations (e.g., involving IgH locus) and mutations (e.g., ras, p53).
• Assessment of angiogenesis as a prognostic factor and its response to thalidomide therapy.

Main Results:

• HHV-8 is detectable in most myeloma patients' peripheral blood, with variations in ORF sequences between patients.
• Consistent expression of viral IRF and IL-8R homologs suggests a role in myeloma pathogenesis.
• Myeloma is characterized by frequent chromosome translocations (11q13, 4p16, 16q23), ras mutations, and monosomy 13q.
• Angiogenesis increases with disease progression and may be reversed by thalidomide.

Conclusions:

• HHV-8 may play a role in multiple myeloma development or progression.
• Specific chromosomal abnormalities and mutations are hallmarks of multiple myeloma.
• Angiogenesis is a significant prognostic factor in multiple myeloma, with potential therapeutic implications.