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Prognostic significance of BAD and AIF apoptotic pathways in diffuse large B-cell lymphoma.

Abstract : BACKGROUND: To determine whether proapoptotic proteins were associated with clinicopathologic heterogeneity and influenced survival in patients with diffuse large B-cell lymphoma (DLBCL), we evaluated patterns of expression of the BCL-2 family member BAD, PP1alpha (the catalytic subunit of PP1 involved in activation of BAD), and apoptosis-inducing factor (AIF). PATIENTS AND METHODS: We retrospectively analyzed 46 patients all treated with standard chemotherapy ([CHOP] cyclophosphamide/doxorubicin/vincristine/prednisone-like); of these, 16 received rituximab. Immunohistochemical analyses were performed from biopsy samples of nodal DLBCL that were performed at initial diagnosis. Normal reactive lymph nodes were used as controls. RESULTS: BAD expression was found in 38 of 46 DLBCL cases and, though variable, was often strong. PP1alpha and AIF were detected in all tumors tested with a relative strong expression. Lower BAD expression was shown to be significantly associated with advanced clinical stages (Ann Arbor stage III + IV and International Prognostic Index intermediate-high to high; P = .006 and P = .0008, respectively). Moreover, BAD staining was positively correlated with BCL-2 (P = .022) and PP1alpha (P = .013) staining. Finally, high AIF expression proved to be predictive of a longer overall survival in non-rituximab-treated patients. CONCLUSION: Our study shows for the first time in DLBCL that differential BAD expression might play a role in the development of the disease, possibly reflecting its function as a tumor suppressor. Furthermore, our data highlight the interest in targeting BAD phosphatases and AIF-mediated mitochondrial apoptosis for new therapeutic strategies.
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Submitted on : Wednesday, June 1, 2011 - 3:16:49 PM
Last modification on : Tuesday, April 5, 2022 - 3:44:49 AM

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Danielle Troutaud, Barbara Petit, Cynthia Bellanger, Benoît Marin, Marie-Pierre Gourin-Chaury, et al.. Prognostic significance of BAD and AIF apoptotic pathways in diffuse large B-cell lymphoma.. Clinical Lymphoma, Myeloma & Leukemia, Elsevier, 2010, 10 (2), pp.118-24. ⟨10.3816/CLML.2010.n.016⟩. ⟨hal-00597660⟩

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