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

Blood. 2001 Aug 15;98(4):945-51. doi: 10.1182/blood.v98.4.945.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is characterized by a marked degree of morphologic and clinical heterogeneity. Establishment of parameters that can predict outcome could help to identify patients who may benefit from risk-adjusted therapies. BCL-6 is a proto-oncogene commonly implicated in DLBCL pathogenesis. A real-time reverse transcription-polymerase chain reaction assay was established for accurate and reproducible determination of BCL-6 mRNA expression. The method was applied to evaluate the prognostic significance of BCL-6 expression in DLBCL. BCL-6 mRNA expression was assessed in tumor specimens obtained at the time of diagnosis from 22 patients with primary DLBCL. All patients were subsequently treated with anthracycline-based chemotherapy regimens. These patients could be divided into 2 DLBCL subgroups, one with high BCL-6 gene expression whose median overall survival (OS) time was 171 months and the other with low BCL-6 gene expression whose median 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 predicted longer OS in patients with DLBCL. BCL-6 gene expression was an independent survival predicting factor in multivariate analysis together with the elements 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 expression should be considered a new favorable prognostic factor in DLBCL and should be used in the stratification and the design of risk-adjusted therapies for patients with DLBCL. (Blood. 2001;98:945-951)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / analysis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / standards
  • Disease-Free Survival
  • Gene Expression
  • Germinal Center / chemistry
  • Humans
  • Immunohistochemistry
  • Lymphoma, B-Cell / chemistry
  • Lymphoma, B-Cell / diagnosis*
  • Lymphoma, B-Cell / mortality*
  • Lymphoma, Large B-Cell, Diffuse / chemistry
  • Lymphoma, Large B-Cell, Diffuse / diagnosis*
  • Lymphoma, Large B-Cell, Diffuse / mortality*
  • Methods
  • Middle Aged
  • Polymerase Chain Reaction
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / standards
  • Proto-Oncogene Proteins c-bcl-6
  • Reproducibility of Results
  • Survival Rate
  • Transcription Factors / genetics*
  • Transcription Factors / standards

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Transcription Factors