BCL-6 protein is expressed in precursor T-cell lymphoblastic lymphoma and in prenatal and postnatal thymus

Abstract

The organization and expression of the BCL-6 gene in normal and neoplastic thymic T cells has not been fully determined. We examined 8 precursor T-cell lymphoblastic lymphomas (T-LBLs) and found significant BCL-6 expression in 4 cases. Three of the BCL-6+ cases expressed a common thymocyte phenotype (CD4+, CD8+), and one expressed a precursor thymocyte phenotype (CD4-, CD8-). In 6 cases evaluated, including those expressing BCL-6, molecular analyses demonstrated a germline configuration of the BCL-6 gene and a wild-type BCL-6 gene first exon-intron boundary region. We also evaluated 12 normal prenatal and postnatal thymuses for BCL-6 protein. BCL-6 was expressed by most cortical thymocytes and by scattered medullary thymocytes. BCL-6+ cortical and medullary thymocytes also expressed CD2, CD3, CD4, CD5, CD7, or CD8. We further analyzed the pattern of BCL-2 and BCL-XL expression and their coexpression with BCL-6 in normal thymus and T-LBL and compared it to that of follicle centers of reactive lymph nodes and follicular lymphoma. BCL-6+ cortical thymocytes coexpressed BCL-XL but not BCL-2. All 4 BCL-6+ T-LBLs and 4 BCL-6- T-LBLs coexpressed BCL-2 and BCL-XL. Conceivably, T-LBLs may arise through clonal expansion of cortical thymocytes normally expressing the BCL-6 protein. The pattern of BCL-6, BCL-2, and BCL-XL expression in cortical thymocytes is highly reminiscent of germinal centers, and the abnormal coexpression of BCL-2, BCL-XL, and BCL-6 in T-LBL is analogous to coexpression in follicle center cell lymphomas, suggesting that coexpression of these anti-apoptotic genes may contribute to the pathogenesis of T-LBL. © 2001 by The American Society of Hematology.