Journal
BLOOD
Volume 118, Issue 5, Pages 1350-1358Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-03-345272
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Funding
- National Cancer Institute [P01CA34233, U54CA149145, U56-CA112973, CA109335]
- Dwoskin Family Foundation
- Bankhead-Coley Foundation
- Fidelity Foundation
- Terry Fox Foundation [019001]
- Fondation de France
- Association pour la Recherche sur le Cancer
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Several gene-expression signatures predict survival in diffuse large B-cell lymphoma (DLBCL), but the lack of practical methods for genome-scale analysis has limited translation to clinical practice. We built and validated a simple model using one gene expressed by tumor cells and another expressed by host immune cells, assessing added prognostic value to the clinical International Prognostic Index (IPI). LIM domain only 2 (LMO2) was validated as an independent predictor of survival and the germinal center B cell-like subtype. Expression of tumor necrosis factor receptor superfamily member 9 (TNFRSF9) from the DLBCL microenvironment was the best gene in bivariate combination with LMO2. Study of TNFRSF9 tissue expression in 95 patients with DLBCL showed expression limited to infiltrating T cells. A model integrating these 2 genes was independent of cell-of-origin classification, stromal signatures, IPI, and added to the predictive power of the IPI. A composite score integrating these genes with IPI per-formed well in 3 independent cohorts of 545 DLBCL patients, as well as in a simple assay of routine formalin-fixed specimens from a new validation cohort of 147 patients with DLBCL. We conclude that the measurement of a single gene expressed by tumor cells (LMO2) and a single gene expressed by the immune microenvironment (TNFRSF9) powerfully predicts overall survival in patients with DLBCL. (Blood. 2011; 118(5): 1350-1358)
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