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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3818-3826. Prepublished online as a Blood First Edition Paper on August 5, 2008; DOI 10.1182/blood-2008-02-138933. This Article Full Text (PDF) All Versions of this Article: blood-2008-02-138933v1 112/9/3818    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Calvo, K. R Articles by Jaffe, E. S Search for Related Content PubMed PubMed Citation Articles by Calvo, K. R Articles by Jaffe, E. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 27, 2008 Accepted June 28, 2008 IL-4 protein expression and basal activation of Erk in vivo in follicular lymphoma Katherine R Calvo*, Bhavana Dabir, Alexandra Kovach, Christopher Devor, Russell Bandle, Amelia Bond, Joanna H Shih, and Elaine S Jaffe Laboratory of Pathology, National Cancer Institute, Bethesda, MD, United States Clinical Proteomics Core Lab, National Cancer Institute, Bethesda, MD, United States Division of Cancer Treatment and Diagnosis Biometric Research Branch, National Cancer Institute, Bethesda, MD, United States * Corresponding author; email: calvok{at}mail.nih.gov. Follicular lymphoma (FL) is characterized by constitutive expression of Bcl-2 as a consequence of t(14;18). Evidence suggests factors in the lymph node microenvironment, related to intratumoral T-cells, macrophages, and dendritic cells, play a role in the disease process. We generated proteomic cytokine profiles of FL (N=50) and follicular hyperplasia (FH; N=23). Ten cytokines were assayed using ultrasensitive multiplex elisas: IL-1beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-13, IL-12p70, TNF-alpha, and INF-gamma. Each cytokine showed overall lower protein concentrations in FL, with the exception of IL-4, which was nearly 5 times higher in FL than FH (p= 0.0054). Using reverse-phase protein microarrays (RPMA), we evaluated the activation state of several intracellular signaling proteins downstream of cytokine receptors. Basal Erk phosphorylation was approximately 4 times greater in FL than FH (p < 0.0001) with similar findings for Mek; Stat-6 showed weak basal phosphorylation that was approximately twice as high in FL than in FH (p = 0.012). In conclusion, the FL microenvironment contains increased levels of IL-4, with prominent tumor basal phosphorylation of Erk. These findings suggest IL-4, Erk, and possibly Stat-6 may play a role in the biology of FL and may serve as targets for future therapies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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