Expression of a single gene, BCL-6, strongly predicts survival in patients with diffuse large B-cell lymphoma.
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)
Lossos
I S
IS
Department of Medicine, Division of Oncology, Stanford University Medical Center, CA 94305-5151, USA.
Jones
C D
CD
Warnke
R
R
Natkunam
Y
Y
Kaizer
H
H
Zehnder
J L
JL
Tibshirani
R
R
Levy
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000592:standards; D018572:Disease-Free Survival; D015870:Gene Expression; D018858:Germinal Center / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality*; D008722:Methods; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000592:standards; D051560:Proto-Oncogene Proteins c-bcl-6; D015203:Reproducibility of Results; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics* / Q000592:standards
D015415:Biomarkers; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors