Chemokine RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted) in Multiple Myeloma and MGUS (Monoclonal Gammopathy of Undetermined Significance).

Introduction: Bone disease in patients with myeloma is the devastating complication. RANTES (CCR chemokine, Regulated upon Activation,Normal T Cell Expressed and Secreted) is involved in the bone remodeling that is made by coupled functions of osteoclasts and osteoblasts. Osteoclasts represent the RANTES receptor CCR1 and product RANTES. Osteoblasts express CCR1,3,4,5, and also product RANTES. Osteoblasts chemotaxicaly move to osteoclasts to repair the absorbed bone lesions (Shozo Yano et al., Endocrinology Vol.145, No.5, 2324–2335). The bone pathophysiology of multiple myeloma is the distortion of the well-balanced functions of osteoclast and osteobast. The change of RANTES may be representative of this distortion and the restoration of bone.

Method: Blood samples were collected from 54 patients with Multiple Myeloma, 15 patients with MGUS, 41 from donors (30 healthy people or 11 people who have no bone disease). Plasma samples were separated and analyzed by ELISA to determine the levels of RANTES.

Result: In healthy people, RANTES changes in proportion to ages with sexual difference. The value of RANTES is 155000pg/ml in20ys male, 51100pg/ml in 20ys female, 133000pg/ml in 40ys male and 78933 pg/ml in 40ys female. The difference of male and female becomes smaller and the value becomes nearly 60000pg/ml at sixty ages in male and female. Serum-bone specific alkaline phosphatase (BAP) is a biochemical indicator of bone turnover and urinary collagen type 1 cross-linked N-telopeptide (NTX) excretion normalized to creatinine (NTX/Cr) from urine sample is a bone resorption marker. At sixty ages, BAP and NTX/Cr become lower in accord with RANTES. In Myeloma cases, RANTES is about 20000pg/ml lower than the age-related value in female and about 75000pg/ml higher in male. After the treatment, RANRES increases in most of patients (both male and female) who have got response after chemotherapy. The rise of female is average 34566pg/ml but the rise of male is very small, average 5250pg/ml, because RANTES has already increased before chemotherapy. Beyond our expectation,RANTES of MGUS is almost the same as Myeloma.

Discussion: The bone remodeling activity of male is higher than female and may be easily induced by the chance of bone absorption. The data suggest that tumor growth suppression produces the recovery of the remodeling. The value of RANTES of MGUS indicates why some patients with MGUS have the punched-out lesions like Myeloma.

Conclusion: This study has turned out for the first time that RANTES is associated with the bone pathophysiology of multiple myeloma and MGUS.