Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment

Ash A. Alizadeh, Andrew J. Gentles, Alvaro J. Alencar, Chih Long Liu, Holbrook E. Kohrt, Roch Houot, Matthew J. Goldstein, Shuchun Zhao, Yasodha Natkunam, Ranjana H. Advani, Randy D. Gascoyne, Javier Briones, Robert J. Tibshirani, June H. Myklebust, Sylvia K. Plevritis, Izidore Lossos, Ronald Levy

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1350-1358
Number of pages9
JournalBlood
Volume118
Issue number5
DOIs
StatePublished - Aug 4 2011

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Tumor Microenvironment
Lymphoma, Large B-Cell, Diffuse
CD137 Antigens
Tumors
Genes
Cells
Gene Expression
Survival
B-Lymphocytes
Cellular Microenvironment
Germinal Center
T-cells
Transcriptome
Formaldehyde
Neoplasms
Gene expression
Assays
Genome
T-Lymphocytes
Tissue

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Alizadeh, A. A., Gentles, A. J., Alencar, A. J., Liu, C. L., Kohrt, H. E., Houot, R., ... Levy, R. (2011). Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment. Blood, 118(5), 1350-1358. https://doi.org/10.1182/blood-2011-03-345272

Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment. / 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; Levy, Ronald.

In: Blood, Vol. 118, No. 5, 04.08.2011, p. 1350-1358.

Research output: Contribution to journalArticle

Alizadeh, AA, Gentles, AJ, Alencar, AJ, Liu, CL, Kohrt, HE, Houot, R, Goldstein, MJ, Zhao, S, Natkunam, Y, Advani, RH, Gascoyne, RD, Briones, J, Tibshirani, RJ, Myklebust, JH, Plevritis, SK, Lossos, I & Levy, R 2011, 'Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment', Blood, vol. 118, no. 5, pp. 1350-1358. https://doi.org/10.1182/blood-2011-03-345272
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 ; Levy, Ronald. / Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment. In: Blood. 2011 ; Vol. 118, No. 5. pp. 1350-1358.
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