Serum YKL-40 concentrations in newly diagnosed multiple myeloma patients and YKL-40 expression in malignant plasma cells

Objectives: A potential role in cancer biology is suggested for YKL-40 (CHI3L1, HC gp-39). The purpose of this study was to evaluate the clinical value of serum YKL-40 (sYKL-40) in multiple myeloma (MM) and to examine YKL-40 expression in malignant plasma cells (MM PCs). Methods: sYKL-40 was measured by enzyme-linked immunosorbent assay (ELISA) in 82 patients with newly diagnosed MM. YKL-40 expression in immunophenotypically defined plasma cells was investigated by double-labelled immunohistochemistry in 21 MM patients and by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in cDNA archives generated by global RT-PCR in seven controls, 14 patients with monoclonal gammopathy of undetermined significance (MGUS), 45 MM patients, nine patients with extramedullary myeloma (exMM), and seven human myeloma cell lines (HMCLs). Results: sYKL-40 was elevated above a constructed reference range for healthy controls in 29% of the patients investigated. Patients with elevated sYKL-40 had reduced overall survival and event-free survival when compared to patients with normal sYKL-40, but sYKL-40 level was defeated by beta(2)-microglobulin in the multivariate analyses. Intramedullary MM PCs lacked significant expression of YKL-40, but high levels of YKL-40 expression were seen in extramedullary MM PCs from one exMM patient and in six HMCLs. Further investigations of other bone marrow (BM) cells showed YKL-40 expression in megakaryocytes, neutrophils and adherent cells from long-term BM cultures. Conclusions: In newly diagnosed MM-patients, a sYKL-40 elevated above the reference range predicts a poor clinical outcome, and YKL-40 is expressed by other BM cells than MM PCs. At this point, routine measurements of sYKL-40 are not warranted, but YKL-40 should be considered as a potential player in the pathophysiology of MM.