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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.

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NEOPLASIA

Fibromodulin, an extracellular matrix protein: characterization of its unique gene and protein expression in B-cell chronic lymphocytic leukemia and mantle cell lymphoma

Eva Mikaelsson, Amir Hossein Danesh-Manesh, Alfred Lüppert, Mahmood Jeddi-Tehrani, Mohammad-Reza Rezvany, Ramazan Ali Sharifian, Reza Safaie, Azam Roohi, Anders Österborg, Fazel Shokri, Håkan Mellstedt, and Hodjattallah Rabbani

From the Immune and Gene Therapy Laboratory, CCK, and the Departments of Oncology (Radiumhemmet) and Hematology, Karolinska University Hospital, Stockholm, Sweden; the Department of Immunology, Avesina Research Center, Tehran, Iran; the Clinic of Hematology and Oncology, School of Medicine, and the Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Iran; and the National Cell Bank of Iran, Pasteur Institute of Iran, Tehran.

Fibromodulin is an extracellular matrix protein normally produced by collagen-rich tissues; the fibromodulin gene has been found to be the most overexpressed gene in B-cell chronic lymphocytic leukemia. In this study, fibromodulin was expressed at the gene level (reverse transcription-polymerase chain reaction [RT-PCR]) in all patients with B-CLL (n = 75) and in most (5 of 7) 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 after in vitro cultivation, but not at the cell surface. Fibromodulin was not found in patients with T-cell chronic lymphocytic leukemia (T-CLL), B-cell prolymphocytic leukemia (B-PLL), T-cell prolymphocytic leukemia (T-PLL), hairy cell leukemia, follicular lymphoma, lymphoplasmacytic lymphoma, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), or chronic myelogenous leukemia (CML) or in 36 hematologic cell lines. Normal blood mononuclear cells (T and B lymphocytes, monocytes), tonsil B cells, and granulocytes did not express fibromodulin. Activation (phorbol 12-myristate 13-acetate [PMA]/ionomycin) of normal T and B lymphocytes induced 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 unknown. However, its unique protein expression makes it likely that fibromodulin is involved in the pathobiology of B-CLL and MCL. (Blood. 2005;105:4828-4835)


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