TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues

AIDS-related non-Hodgkin's lymphoma (AIDS NHL) comprises a diverse and hete rogeneous group of high-grade B cell tumors. Certain classes of AIDS NHL ar e associated with alterations in oncogenes or tumor-suppressor genes or inf ections by oncogenic herpesviruses. However, the clinically significant cla ss of AIDS NHL designated immunoblastic lymphoma plasmacytoid (AIDS IBLP) l acks any consistent genetic alterations, We identified the TCL1 oncogene fr om a set of AIDS IBLP-associated cDNA fragments generated by subtractive hy bridization with non-AIDS IBLP, Aberrant TCL1 expression has been implicate d in T cell leukemia/lymphoma development, and its expression also has been seen in many established B cell tumor lines. However, TCL1 expression has not been reported in AIDS NHL, We find that TCL1 is expressed in the majori ty of AIDS IBLP tumors examined. TCL1 protein expression is restricted to t umor cells in AIDS IBLP tissue samples analyzed with immunohistochemical st aining. Hyperplastic lymph node and tonsil also exhibit strong TCL1 protein expression in mantle zone B cells and in rare interfollicular zone cells, whereas follicle-center B cells (centroblasts and centrocytes) show weaker expression. These results establish TCL1 as the most prevalent of all of th e surveyed oncogenes associated,vith AIDS IBLP, They also indicate that abu ndant TCL1 expression in quiescent mantle zone B cells is down-regulated in activated germinal center follicular B cells in parallel to the known expr ession pattern of BCL-2 High-level expression in nonproliferating B cells s uggests that TCL1 may function in protecting naive preactivated B cells fro m apoptosis.