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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4828-4835. Prepublished online as a Blood First Edition Paper on March 1, 2005; DOI 10.1182/blood-2004-10-3941.
Submitted October 13, 2004
Immune and Gene Therapy Lab, CCK, Karolinska University Hospital, Stockholm, Sweden * Corresponding author; email: hakan.mellstedt{at}karolinska.se.
Fibromodulin is an extracellular matrix protein normally produced by collagen-rich tissues. By studying the global gene expression profile of B-cell chronic lymphocytic leukemia (B-CLL) cells, fibromodulin was found to be the most over-expressed (>300-2200 times) gene1,2.
In this study, fibromodulin was found to be expressed at the gene level (RT-PCR) in all B-CLL patients (n=75) and in the majority (5/7) of patients with mantle cell lymphoma (MCL). No mutations in the fibromodulin gene were detected. Fibromodulin was also detected at the protein level in the cytoplasm of the B-CLL cells and in the supernatant following in vitro cultivation, but not at the cell surface. Fibromodulin was not found in T-CLL, B-PLL, T-PLL, hairy cell leukemia, follicular lymphoma, lymphoplasmacytic lymphoma, multiple myeloma, ALL, AML, CML and in 36 hematological cell lines. Normal blood mononuclear cells (T and B lymphocytes, monocytes), tonsil B cells and granulocytes did not express fibromodulin. Activation (PMA/ionomycin) of normal T and B lymphocytes induced a weak fibromodulin gene expression but not to the extent seen in freshly isolated B-CLL cells. The reason for the exclusive ectopic expression of fibromodulin in B-CLL and MCL is not known. However, the unique protein expression makes it likely that fibromodulin is involved in the pathobiology of B-CLL and MCL.
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