Semaphorin 4D correlates with increased bone resorption, hypercalcemia, and disease stage in newly diagnosed patients with multiple myeloma.

Abstract

Multiple myeloma (MM) is characterized by bone destruction due to increased bone resorption and decreased bone formation. Semaphorin 4D (CD100, Sema4D) is expressed by osteoclasts, binds to its receptor Plexin-B1, and acts as a mediator of osteoclast-osteoblast interaction that ultimately inhibits osteoblastic bone formation. Preclinical data suggest that Sema4D/Plexin-B1 pathway is implicated in MM-induced bone disease. However, there is no information on the role of Sema4D in MM patients. Thus, we evaluated Sema4D and Plexin-B1 in six myeloma cells lines in vitro; in the bone marrow plasma (BMP) and serum of 72 newly diagnosed symptomatic MM (NDMM) patients and in 25 healthy controls. Only one myeloma cell line produced high Sema4D. BMP and circulating Sema4D and Plexin-B1 levels were significantly higher in MM patients compared to controls (p < 0.01). Sema4D correlated with serum calcium levels (p < 0.001), increased bone resorption (as assessed by CTX; p < 0.01), and ISS (p < 0.001). There was a trend for higher Sema4D levels in patients with osteolysis (p = 0.07), while patients with diffuse MRI pattern had higher BMP Sema4D levels (p = 0.02). Our data suggest that Sema4D is elevated in MM patients and correlate with adverse myeloma features and increased bone resorption, providing a possible target for novel therapeutic approaches in MM.

• Authors: Evangelos Terpos, Ioannis Ntanasis-Stathopoulos, Dimitrios Christoulas, Tina Bagratuni, Marios Bakogeorgos, Maria Gavriatopoulou, Evangelos Eleutherakis-Papaiakovou, Nikolaos Kanellias, Efstathios Kastritis, Meletios A Dimopoulos
• Journal: Blood cancer journal (Blood Cancer J) Vol. 8 Issue 5 Pg. 42 (05 11 2018) ISSN: 2044-5385 [Electronic] United States
• PMID: 29748532 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• Biomarkers
• CD100 antigen
• Nerve Tissue Proteins
• PLXNB1 protein, human
• Receptors, Cell Surface
• Semaphorins

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, CD (blood, genetics)
• Biomarkers
• Female
• Humans
• Hypercalcemia (diagnosis, etiology)
• Magnetic Resonance Imaging (methods)
• Male
• Middle Aged
• Multiple Myeloma (blood, complications, diagnostic imaging, pathology)
• Neoplasm Staging
• Nerve Tissue Proteins (blood)
• Osteolysis (diagnosis, etiology)
• Receptors, Cell Surface (blood)
• Semaphorins (blood, genetics)