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Lymphoma

The expression of 16 genes related to the cell of origin and immune response predicts survival in elderly patients with diffuse large B-cell lymphoma treated with CHOP and rituximab

Leukemia volume 22, pages 1917–1924 (2008)Cite this article

Abstract

Gene expression profiles have been associated with clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-containing chemotherapy. Using Affymetrix HU133A microarrays, we analyzed the lymphoma transcriptional profile of 30 patients treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and 23 patients treated with rituximab (R)-CHOP in the Groupe d'Etude des Lymphomes de l'Adulte clinical centers. We used this data set to select transcripts showing an association with progression-free survival in all patients or showing a differential effect in the two treatment groups. We performed real-time quantitative reverse transcription-PCR in the 23 R-CHOP samples of the screening set and an additional 44 R-CHOP samples set to evaluate the prognostic significance of these transcripts. In these 67 patients, the level of expression of 16 genes and the cell-of-origin classification were significantly associated with overall survival, independently of the International Prognostic Index. A multivariate model comprising four genes of the cell-of-origin signature (LMO2, MME, LPP and FOXP1) and two genes related to immune response, identified for their differential effects in R-CHOP patients (APOBEC3G and RAB33A), demonstrated a high predictive efficiency in this set of patients, suggesting that both features affect outcome in DLBCL patients receiving immunochemotherapy.

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Acknowledgements

We are grateful to Fabien Petel (Ligue Nationale Contre le Cancer) for the management of the Affymetrix and annotation databases and submission of the same to the Array Express. We thank E Jacquet, H Lévaique, E Garrido (CNRS, Gif sur Yvette, France) and E Côme for the realization of the TLDA experiments; A Allain and N Nio for their help in clinical data management. We are indebted to the pathologists and clinicians of the GELA who contributed pathological specimen and clinical data. This study was supported by grants of the Ligue Nationale Contre le Cancer (programme Carte d'Identité des Tumeurs), the Programme Hospitalier de Recherche Clinique (AOM 03060) and an unrestricted grant from Roche.

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Authors and Affiliations

  1. Service de Biostatistique, AP-HP, hôpital Necker, Paris, France

    J-P Jais

  2. Faculté de Médecine, Université Paris Descartes, Paris, France

    J-P Jais & T J Molina

  3. Service d'Hématologie Clinique and Département de Pathologie, AP-HP, hôpital Henri Mondor; Université Paris 12,

    C Haioun, F Reyes, P Gaulard & K Leroy

  4. Université Paris 12, Créteil, France

    C Haioun, F Reyes, P Gaulard & K Leroy

  5. Département de Pathologie, AP-HP, hôpital Hôtel-Dieu, Paris, France

    T J Molina

  6. Programme CIT, Ligue Nationale Contre le Cancer, Paris, France

    D S Rickman & A de Reynies

  7. Service d'Hématologie and Service d'Anatomo-Pathologie, Hospices Civils de Lyon,

    F Berger, B Coiffier & G Salles

  8. Université Lyon 1; UMR CNRS 5239, Pierre-Bénite, France

    F Berger, B Coiffier & G Salles

  9. Service d'Hématologie and Département de Pathologie, AP-HP, hôpital Saint-Louis,

    C Gisselbrecht & J Brière

  10. Université Paris 7, Paris, France

    C Gisselbrecht & J Brière

  11. INSERM, Unité 841, IMRB, équipe no. 9, Créteil, France

    P Gaulard & K Leroy

  12. Service d'Hématologie and Département de Pathologie, hôpitaux de Brabois, Vandoeuvre les Nancy, France

    P Feugier & E Labouyrie

  13. Service d'Hématologie and d'Oncologie Moléculaire, Centre Henri Becquerel, Rouen, France

    H Tilly & C Bastard

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Jais, JP., Haioun, C., Molina, T. et al. The expression of 16 genes related to the cell of origin and immune response predicts survival in elderly patients with diffuse large B-cell lymphoma treated with CHOP and rituximab. Leukemia 22, 1917–1924 (2008). https://doi.org/10.1038/leu.2008.188

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