CCL5 (RANTES) Is Suspected to Be the Key Chemokine to Understand the Bone Pathology of Multiple Myeloma

Background: It has been shown that CCL5 recruits Osteoclasts and Osteoblasts to active bone turnover regions to maintain bone remodeling. In healthy volunteers, CCL5 is higher in male than in female. Although CCL5 is highest in 20ys men, it becomes same level at 60ys in both male and female. These results suggest that the value of CCL5 correlates with the activity of the bone metabolism. In this study, we examined the significance of CCL5 level in MM, which may provide new insights in the bone pathology of this disease.

Patients and Methods: fourteen MM were enrolled in our study. Twelve were newly diagnosed and 2 were relapsed patients. We evaluated CCL5(serum) and bone alkaline phosphatase(BAP, serum), as well as type-I collagen N-telopeptide(NTX, urine) when patients were diagnosed and after the treatment. Regimens of the treatment are

1. Thalidomide 200mg/day and Dexamethasone(Dex) 40mg every 8th day within 21 days cycle,

2. Velcade 1.3mg/m2 on days 1, 4, 8, 11 of a 3 weekly cycle with Dex 40mg,

3. combination of Thalidomide, Velcade and Dex.

Result: We compare CCL5 of 60ys healthy volunteers, ITP patients, Stage 1 MM, Stage2 MM and Stage3 MM. We found highest CCL5 level in Stage 3 MM. Interestingly, BAP was almost same level between Stage1 and Stage3; however NTX level is higher in Stage3 than in Stage1, suggesting that increased CCL5 in Stage3 was predominantly from activated osteoclasts. Importantly increased CCL5 and BAP were recognized in patients who had CR or PR. Moreover, the increase of the number of megakaryocyts in the bone marrow was recognized in 7 patients. These megakaryocytes were strongly stained with anti-CCL5 Ab, suggesting that successful MM treatments could increase production of CCL5 by megakaryocytes.

Conclusion: CCL5 of Osteoclasts in active myeloma contributes bone resorption. On the other hand, in successfuly treated myeloma, CCL5 is produced by megakaryocytes which make Osteoblasts activate. CCL5 may be a novel marker of bone disease in myeloma.