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Blood, 15 January 2008, Vol. 111, No. 2, pp. 806-815. Prepublished online as a Blood First Edition Paper on October 12, 2007; DOI 10.1182/blood-2007-07-101139.
Submitted July 12, 2007
Department of Oncology, St. Olavs University Hospital, Trondheim, Norway * Corresponding author; email: unn-merete.fagerli{at}ntnu.no.
Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cells (PCs) in the bone marrow (BM). Gene expression profiling of two MM cell lines (OH-2 and IH-1) indicated that expression of PRL-3, a metastasis-associated tyrosine phosphatase, was induced by several mitogenic cytokines. Cytokine-driven PRL-3 expression could be shown in several myeloma cell lines both at the mRNA and protein level. There was significantly higher expression of the PRL-3 gene in PCs from patients with Monoclonal Gammopathy of Undetermined Significance (MGUS), Smouldering myeloma (SMM) and myeloma than in normal PCs. Among 7 MM subgroups identified by unsupervised hierarchical cluster analysis, PRL-3 gene expression was significant higher in the 3 groups denoted as Proliferation, Low Bone Disease, and MMSET/FGFR3. PRL-3 protein was detected in 18 out of 20 BM biopsies from patients with MM. Silencing of the PRL-3 gene by siRNA reduced cell migration in the MM cell line INA-6, but had no detectable effect on proliferation and cell cycle phase distribution of the cells. In conclusion, PRL-3 is a gene product specifically expressed in malignant plasma cells and may have a role in migration of these cells.
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