Correspondence

Molecular Outcome Prediction in Diffuse Large-B-Cell Lymphoma

N Engl J Med 2009; 360:2794-2795June 25, 2009

Article

To the Editor:

Lenz et al. (Nov. 27 issue)1 report the results of an important study of gene expression and survival in patients with diffuse large-B-cell lymphoma. We reassessed the performance of a survival predictor that we had previously reported2 by applying it to the expression profiles of tumors from patients described by Lenz et al. Our model performed well in predicting overall survival in these patients, whether they were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or with CHOP in combination with rituximab (R-CHOP) (P<0.001) (Figure 1Figure 1Prediction of Outcome with the Six-Gene Model among Patients with Diffuse Large-B-Cell Lymphoma Treated with CHOP or R-CHOP.). Furthermore, when risk was in the model as a continuous variable, this model, which used the expression levels of only six genes, distinguished risk groups nearly as well as the survival predictor proposed by Lenz et al., which incorporated stromal-cell signatures. Three of the 6 genes in our model (LMO2 [LIM domain only 2 (rhombotin-like 1)], BCL6 [B-cell chronic lymphocytic leukemia/lymphoma 6], and FN1 [fibronectin 1]) are also represented in the prediction model of Lenz et al.; however, the latter requires the measurement of nearly 400 genes in fresh or frozen tumor specimens. Furthermore, our model is a robust predictor of outcomes in other cohorts of patients treated with CHOP or R-CHOP regimens, regardless of the type of diagnostic specimen obtained and the method of measurement used.3 Our prediction model is simple, robust, and applicable to routinely obtained diagnostic specimens that are formalin-fixed and paraffin-embedded.

Ash A. Alizadeh, M.D., Ph.D.
Andrew J. Gentles, Ph.D.
Izidore S. Lossos, M.D.
Ronald Levy, M.D.
Stanford University School of Medicine, Stanford, CA 94305
arasha@stanford.edu

Drs. Alizadeh, Lossos, and Levy report holding a patent for the classification of patients with diffuse large-B-cell lymphoma based on gene expression. No other potential conflict of interest relevant to this letter was reported.

3 References

1. 1

   Lenz G, Wright G, Dave SS, et al. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 2008;359:2313-2323
   Full Text | Web of Science | Medline

2. 2

   Lossos IS, Czerwinski DK, Alizadeh AA, et al. Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N Engl J Med 2004;350:1828-1837
   Full Text | Web of Science | Medline

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   Malumbres R, Chen J, Tibshirani R, et al. Paraffin-based 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP. Blood 2008;111:5509-5514
   CrossRef | Web of Science | Medline

Citing Articles (6)

Citing Articles

1. 1

   A. A. Alizadeh, A. J. Gentles, A. J. Alencar, C. L. Liu, H. E. Kohrt, R. Houot, M. J. Goldstein, S. Zhao, Y. Natkunam, R. H. Advani, R. D. Gascoyne, J. Briones, R. J. Tibshirani, J. H. Myklebust, S. K. Plevritis, I. S. Lossos, R. Levy. (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
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   S. Montes-Moreno, N. Martinez, B. Sanchez-Espiridion, R. Diaz Uriarte, M. E. Rodriguez, A. Saez, C. Montalban, G. Gomez, D. G. Pisano, J. F. Garcia, E. Conde, E. Gonzalez-Barca, A. Lopez, M. Mollejo, C. Grande, M. A. Martinez, C. Dunphy, E. D. Hsi, G. B. Rocque, J. Chang, R. S. Go, C. Visco, Z. Xu-Monette, K. H. Young, M. A. Piris. (2011) miRNA expression in diffuse large B-cell lymphoma treated with chemoimmunotherapy. Blood 118:4, 1034-1040
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   Christof Schneider, Laura Pasqualucci, Riccardo Dalla-Favera. (2011) Molecular pathogenesis of diffuse large B-cell lymphoma. Seminars in Diagnostic Pathology 28:2, 167-177
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   Blanca Xicoy, Josep-Maria Ribera, José-luís Mate, Gustavo Tapia, Mireia Morgades, José-Tomás Navarro, Carolina Sanz, Aurelio Ariza, Evarist Feliu. (2010) Immunohistochemical expression profile and prognosis in patients with diffuse large B-cell lymphoma with or without human immunodeficiency virus infection. Leukemia & Lymphoma 51:11, 2063-2069
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   F. Jardin, J.-P. Jais, T.-J. Molina, F. Parmentier, J.-M. Picquenot, P. Ruminy, H. Tilly, C. Bastard, G.-A. Salles, P. Feugier, C. Thieblemont, C. Gisselbrecht, A. de Reynies, B. Coiffier, C. Haioun, K. Leroy. (2010) Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study. Blood 116:7, 1092-1104
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   Alexandra Smith, Eve Roman, Debra Howell, Richard Jones, Russell Patmore, Andrew Jack, . (2010) The Haematological Malignancy Research Network (HMRN): a new information strategy for population based epidemiology and health service research. British Journal of Haematology 148:5, 739-753
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