Regulation of TCL1 expression in B- and T-cell lymphomas and reactive lymphoid tissues

Chromosomal rearrangements observed in T-cell prolymphocytic leukemia invol ve the translocation of one T-cell receptor gene to either chromosome 14q32 or Xq28, deregulating the expression of cellular protooncogenes of unknown function, such as TCL1 or its homologue, MTCP1, In the human hematopoietic system, TCL1 expression is predominantly observed in developing B lymphocy tes, whereas its overexpression in T cells causes mature T-cell proliferati on in transgenic mice. In this study, using a newly generated monoclonal an tibody against recombinant TCL1 protein, we extended our analysis mainly by immunohistochemistry and also by fluorescence-activated cell sorting and W estern blot to a large tumor lymphoma data bank including 194 cases of lymp hoproliferative disorders of B- and T-cell origin as well as reactive lymph oid tissues. The results obtained show that in reactive lymphoid tissues, T CL1 is strongly expressed by a subset of mantle zone B lymphocytes and is e xpressed to a lesser extent by follicle center cells and by scattered inter follicular small lymphocytes, In B-cell neoplasia, TCL1 was expressed in th e majority of the cases, including lymphoblastic Lymphoma, chronic Lymphocy tic leukemia, mantle cell lymphoma, follicular lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma (60%), and primary cutaneous B cell lymphoma (55%), TCL1 expression was observed in both the cytoplasmic and nuclear com partments, as confirmed by Western blot analysis. Conversely, TCL1 was not expressed in Hodgkin/Reed-Sternberg cells, multiple myelomas, marginal zone B-cell lymphomas, CD30(+) anaplastic large cell lymphoma, lymphoblastic T- cell lymphoma, peripheral T-cell lymphoma, and mycosis fungoides. These dat a indicate that TCL1 is expressed in more differentiated B cells, under bot h reactive and neoplastic conditions, from antigen committed B cells and in germinal center B cells and is down-regulated in the latest stage of B-cel l differentiation.