Introduction. The secreted glycoprotein YKL-40 (CHI3L1, HC gp-39) is a potential player in the tumor-host interactions affecting several aspects of multiple myeloma (MM) including bone destruction. Previous studies support a role for YKL-40 in remodelling of the extracellular matrix, in angiogenesis, and in cancer cell survival and invasion. The aim of this study was to investigate the association between serum YKL-40 (S-YKL-40) and the degree of bone disease in MM. Materials and Methods. S-YKL-40 was measured using an ELISA in 54 MM patients at diagnosis. Bone morbidity was assessed by radiography and scored semiquantitative as a total X-ray score. Ongoing bone metabolism was assessed using biochemical markers of bone formation (S-PICP, S-PINP, S-Bone ALP, S-OC) and bone resorption (S-CTX-MMP, U-NTX-1, U-PYD, UDPD). The first 34 patients included were treated with conventional chemotherapy and followed for up to 30 months. Skeletal related events (SRE) were registered and subdivided in vertebral fractures and osteolytic events including non-vertebral fractures. Results. 57% of the patients had a S-YKL-40 elevated above the upper limit in an age specific 90 per cent reference range for healthy adults. Patients with elevated S-YKL-40 had a higher total X-ray score (p=0.005) and higher levels of S-CTX-MMP (p=0.003), U-PYD (p=0.004) and U-DPD (p=0.002), while U-NTX-1 and the markers of bone formation did not differ from the levels seen in patients with normal S-YKL-40. During follow-up 21 patients experienced SRE and 15 patients had osteolytic events. Using S-YKL-40 level, i.e. normal vesrsus elevated patients with elevated S-YKL-40 had shorter time to first osteolytic event (12 months versus not reached; Log rank test =0.03; HR = 3.70; p=0,046. This was confirmed when using S-YKL-40 (log2) as a continuous variable (HR = 1.45; p=0.048). The differences between groups for time to first SRE was only borderline significant. Conclusions. Newly diagnosed MM patients with elevated levels of S-YKL-40 have more severe bone destruction including increased bone resorptive activity and shorter time to progression of myeloma-related bone disease. A potential role for YKL-40 in the bone disease of MM must be considered.
Haematologica, 2007, Vol 92(S2), Issue 6
Main Research Area:
XI<sup>th </sup>International Myeloma Workshop IV<sup>th</sup> International Workshop on Waldenström's Macroglobulinemia, 2007