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Alizadeh, Ash A.; Gentles, Andrew J.; Alencar, Alvaro J.; Liu, Chih Long; Kohrt, Holbrook E.; Houot, Roch; Goldstein, Matthew J.; Zhao, Shuchun; Natkunam, Yasodha; Advani, Ranjana H.; Gascoyne, Randy D.; Briones, Javier; Tibshirani, Robert J.; Myklebust, June H.; Plevritis, Sylvia K.; Lossos, Izidore S.; Levy, Ronald
Blood, 08/2011, Letnik: 118, Številka: 5Journal Article
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 performed 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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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