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

• Published in: Blood Vol. 105; no. 12; pp. 4828 - 4835
• Main Authors: Mikaelsson, Eva, Danesh-Manesh, Amir Hossein, Lüppert, Alfred, Jeddi-Tehrani, Mahmood, Rezvany, Mohammad-Reza, Sharifian, Ramazan Ali, Safaie, Reza, Roohi, Azam, Österborg, Anders, Shokri, Fazel, Mellstedt, Håkan, Rabbani, Hodjattallah
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.06.2005; The Americain Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, CD - biosynthesis; Antigens, CD19 - biosynthesis; Antigens, Differentiation, T-Lymphocyte - biosynthesis; Biological and medical sciences; Biomarkers, Tumor - metabolism; Blotting, Western; CD5 Antigens - biosynthesis; Cell Line, Transformed; Cell Line, Tumor; Coculture Techniques; Collagen - metabolism; Cytoplasm - metabolism; DNA Mutational Analysis; DNA, Complementary - metabolism; Extracellular Matrix - metabolism; Extracellular Matrix Proteins - chemistry; Extracellular Matrix Proteins - metabolism; Female; Fibroblasts - metabolism; Fibromodulin; Flow Cytometry; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Hematologic Neoplasms - metabolism; Humans; Immunoblotting; Lectins, C-Type; Leukemia, B-Cell - metabolism; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Leukemia, T-Cell - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes, Mononuclear - metabolism; Lymphoma, Mantle-Cell - metabolism; Male; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Mutation; Palatine Tonsil - metabolism; Proteoglycans - chemistry; Proteoglycans - metabolism; Receptors, Interleukin-2 - biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Time Factors; Human; Fibromodulin; Chronic; Chronic lymphocytic leukemia; Pathophysiology; Lymphoproliferative syndrome; Mantle cell lymphoma; Gene overexpression; Extracellular matrix; Malignant hemopathy; B-Lymphocyte; Non Hodgkin lymphoma
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-10-3941

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)