title: Fibromodulin, an extracellular matrix protein: characterization of its unique gene and protein expression in B-cell chronic lymphocytic leukemia and mantle cell lymphoma.
abstract: 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.
authors.affiliation: Immune and Gene Therapy Laboratory, CCK, Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Mikaelsson
authors.forename: Amir Hossein
authors.initials: AH
authors.lastname: Danesh-Manesh
authors.forename: Alfred
authors.initials: A
authors.lastname: Lüppert
authors.forename: Mahmood
authors.initials: M
authors.lastname: Jeddi-Tehrani
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Rezvany
authors.forename: Ramazan Ali
authors.initials: RA
authors.lastname: Sharifian
authors.forename: Reza
authors.initials: R
authors.lastname: Safaie
authors.forename: Azam
authors.initials: A
authors.lastname: Roohi
authors.forename: Anders
authors.initials: A
authors.lastname: Osterborg
authors.forename: Fazel
authors.initials: F
authors.lastname: Shokri
authors.forename: Håkan
authors.initials: H
authors.lastname: Mellstedt
authors.forename: Hodjattallah
authors.initials: H
authors.lastname: Rabbani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis; D018941:Antigens, CD19 / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D018956:CD5 Antigens / Q000096:biosynthesis; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D000071235:Fibromodulin; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D037181:Lectins, C-Type; D015448:Leukemia, B-Cell / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism*; D015458:Leukemia, T-Cell / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D014066:Palatine Tonsil / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; D000945:Antigens, Differentiation, T-Lymphocyte; D014408:Biomarkers, Tumor; D018956:CD5 Antigens; D003094:Collagen; D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D000071235:Fibromodulin; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D013755:Tetradecanoylphorbol Acetate; D000099192:CD69 Antigens; C000604330:FMOD protein, human