Abstract #LB-208: Histone deacetylase (HDAC) 3 inhibiton through LBH589 dephosphorylate Akt through protein phosphatase 1 (PP1) complexes in diffuse large B cell Lymphoma

TL;DRAbstract

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO Diffuse large B cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma (NHL) that is considered curable; however, even with rituximab-based chemoimmunotherapy 40% relapse and die of disease. New agents with novel mechanisms of action are needed for this disease. We have demonstrated that treatment of DLBCL cells with the histone deacetylase (HDAC) inhibitor LBH589 as a single agent induced growth inhibition at nano-molar doses in association with inhibition of constitutively activated Akt in a time and dose dependent manner. The aim of the present study is to explore the mechanism by which LBH causes Akt deactivation in DLBCL. Mechanistically, this Akt dephosphorylation might be mediated through the deactivation of upstream kinases or the activation of a downstream phosphatase. To discern the role of transcriptional activation by LBH, we assessed the expression levels of a series of signaling proteins related to the regula

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