Expression of a single gene, BCL-6, strongly predicts survival in patientswith diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is characterized by a marked degree o f morphologic and clinical heterogeneity. Establishment of parameters that can predict outcome could help to identify patients who may benefit from ri sk-adjusted therapies. BCL-6 is a proto-oncogene commonly implicated in DLB CL pathogenesis. A real-time reverse transcription-po lyme rase chain react ion assay was established for accurate and reproducible determination of BC L-6 mRNA expression. The method was applied to evaluate the prognostic sign ificance of BCL-6 expression in DLBCL. BCL-6 mRNA expression was assessed i n tumor specimens obtained at the time of diagnosis from 22 patients with p rimary DLBCL. All patients were subsequently treated with anthracycline-bas ed chemotherapy regimens. These patients could be divided into 2 DLBCL subg roups, one with high BCL-6 gene expression whose median overall survival (O S) time was 171 months and the other with low BCL-6 gene expression whose m edian OS was 24 months (P = .007). BCL-6 gene expression also predicted OS in an independent validation set of 39 patients with primary DLBCL (P = .01 ). BCL-6 protein expression, assessed by immunohistochemistry, also predict ed longer OS in patients with DLBCL. BCL-6 gene expression was an independe nt survival predicting factor in multivariate analysis together with the el ements of the International Prognostic Index (IPI) (P = .038). By contrast, the aggregate IPI score did not add further prognostic information to the patients' stratification by BCL-6 gene expression. High BCL-6 mRNA expressi on should be considered a new favorable prognostic factor in DLBCL and shou ld be used in the stratification and the design of risk-adjusted therapies for patients with DLBCL. (C) 2001 by The American Society of Hematology.