FASN and CD36 predict survival in rituximab-treated diffuse large B-cell lymphoma
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ORIGINAL ARTICLE
FASN and CD36 predict survival in rituximab-treated diffuse large B-cell lymphoma Olga V. Danilova & Larry J. Dumont & Norman B. Levy & Frederick Lansigan & William B. Kinlaw & Alexey V. Danilov & Prabhjot Kaur
Received: 19 June 2012 / Accepted: 7 September 2012 / Published online: 5 October 2012 # Springer-Verlag 2012
Abstract Diffuse large B-cell lymphoma is the most common lymphoid malignancy, as it accounts for approximately one third of all patient cases of non-Hodgkin’s lymphoma. Patients with diffuse large B-cell lymphoma have markedly different treatment outcomes, suggesting a need for reliable prognostic factors and novel therapeutic approaches. De novo fatty acid synthesis is an important metabolic driver of tumor in multiple malignancies. In this retrospective study, we analyzed expression of fatty acid synthase (a key enzyme in de novo fatty acid synthesis), Spot 14 (thyroid hormone responsive Spot 14, a nuclear protein that promotes expression of genes involved in fatty acid synthesis), and CD36 (the cell surface channel for exogenous fatty acid uptake) in patients with diffuse large B-cell lymphoma and their clinical significance. We observed that overexpression of fatty acid synthase is negatively associated with overall survival (p00.001) and progression-free period (p00.004) in patients with diffuse large B-cell lymphoma. Multivariate analysis showed that fatty acid synthase overexpression is Electronic supplementary material The online version of this article (doi:10.1007/s12308-012-0166-4) contains supplementary material, which is available to authorized users. O. V. Danilova : L. J. Dumont : N. B. Levy : P. Kaur (*) Department of Pathology, Dartmouth–Hitchcock Medical Center, Lebanon, NH 03756, USA e-mail: [email protected] F. Lansigan : W. B. Kinlaw : A. V. Danilov Department of Medicine, Dartmouth–Hitchcock Medical Center, Lebanon, NH, USA L. J. Dumont : N. B. Levy : F. Lansigan : W. B. Kinlaw : A. V. Danilov : P. Kaur Geisel School of Medicine at Dartmouth, Hanover, NH, USA N. B. Levy : F. Lansigan : W. B. Kinlaw : A. V. Danilov : P. Kaur Norris Cotton Cancer Center, Lebanon, NH, USA
an independent prognostic marker of aggressive clinical course. For the first time, we report CD36 as an independent protective factor in patients treated with rituximab. Thus, fatty acid synthase and CD36 expression may serve as prognostic markers to predict response to treatment and survival in diffuse large B-cell lymphoma patients. Fatty acid synthase may also be a potential therapeutic target in lymphoid malignancies. Keywords Fatty acid synthase . CD36 . S14 . Lipogenesis . Survival . Diffuse large B-cell lymphoma
Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common malignant lymphoma in the Western world and accounts for 35–40 % of all cases of non-Hodgkin’s lymphoma diagnosed in the USA each year [1]. The biology and pathogenesis of DLBCL remain elusive, and up to 50 % of the patients succumb to their illness despite anthracyclinebased multiagent chemotherapy
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