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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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Submitted October 13, 2004
Accepted February 20, 2005

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

Eva Mikaelsson, Amir H Manesh, Alfred Luppert, Mahmood Jeddi-Tehrani, Mohammad-Reza Rezvany, Ramazan A Sharifian, Reza Safaie, Azam Roohi, Anders Osterborg, Fazel Shokri, Hakan Mellstedt*, and Hodjattallah Rabbani

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

* 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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