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Blood, 15 August 2001, Vol. 98, No. 4, pp. 945-951
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Expression of a single gene, BCL-6, strongly predicts
survival in patients with diffuse large B-cell lymphoma
Izidore S. Lossos,
Carol D. Jones,
Roger Warnke,
Yasodha Natkunam,
Herbert Kaizer,
James L. Zehnder,
Rob Tibshirani, and
Ronald Levy
From the Departments of Medicine, Pathology, and Health
Research and Policy, Division of Oncology, Stanford University Medical
Center, CA.
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.

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