title: TCL1 in B-cell tumors retains its normal b-cell pattern of regulation and is a marker of differentiation stage.
abstract: The high expression of the T-cell oncogene TCL1 in B-cell tumors and the emergence of B-cell lymphomas in TCL1-transgenic mice suggest a pathogenetic role for this kinase coregulator in B-cell malignancies. We compared the expression of TCL1 in B-cell tumors with their differentiation stage. As with normal B-cell subsets, uniform TCL1 expression was characteristic of tumors of pregerminal center derivation such as precursor B-cell lymphoblastic leukemia/lymphoma (85%, 47/55) and mantle cell lymphoma (84%, 49/58), and was more variable in follicular lymphoma (57%, 28/49). Large B-cell lymphoma was less frequently positive for TCL1 (36%, 18/50), especially among cases of the activated B-cell type. All types of Hodgkin lymphoma, splenic marginal zone lymphoma, and post-germinal center-derived tumors, including plasma cell myeloma and MALT lymphoma, were negative for TCL1, except for 1 case. In nearly all TCL1-expressing tumors, as with normal B cells, variations in cellular TCL1 levels were related to the proliferation and microenvironmental factors. In normal B cells, cell lines and primary B-cell tumor samples, TCL1 downmodulation occurred after prolonged cytokine treatment and/or B-cell receptor stimulation. In contrast to mature T-cell tumors where TCL1 expression is always indicative of an activating TCL1 gene translocation, TCL1 expression in B-cell tumors parallels its regulation in non-neoplastic B cells. Therefore, TCL1 expression can be used diagnostically as an indicator of the differentiation stage of a given B-cell tumor.
authors.affiliation: Department of Hematopathology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Herling
authors.forename: Kaushali A
authors.initials: KA
authors.lastname: Patel
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: Kong-Chao
authors.initials: KC
authors.lastname: Chang
authors.forename: George Z
authors.initials: GZ
authors.lastname: Rassidakis
authors.forename: Richard
authors.initials: R
authors.lastname: Ford
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human