Serum YKL-40 concentrations in newly diagnosed multiple myeloma patients and YKL-40 expression in malignant plasma cells.
OBJECTIVE
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.
Mylin
Anne K
AK
Department of Haematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. anne.k.mylin@dadlnet.dk
Rasmussen
Thomas
T
Johansen
Julia S
JS
Knudsen
Lene M
LM
Nørgaard
Peter H
PH
Lenhoff
Stig
S
Dahl
Inger M S
IM
Johnsen
Hans E
HE
D054392:Adipokines; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D000071451:Chitinase-3-Like Protein 1; D018076:DNA, Complementary / Q000096:biosynthesis; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D037102:Lectins; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000473:pathology; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
D054392:Adipokines; D014408:Biomarkers, Tumor; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D018076:DNA, Complementary; D006023:Glycoproteins; D037102:Lectins