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Nuclear FOXO1 promotes lymphomagenesis in germinal center B cells

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Item Type:Article
Title:Nuclear FOXO1 promotes lymphomagenesis in germinal center B cells
Creators Name:Kabrani, E., Chu, V.T., Tasouri, E., Sommermann, T., Baßler, K., Ulas, T., Zenz, T., Bullinger, L., Schultze, J.L., Rajewsky, K. and Sander, S.
Abstract:FOXO1 acts as a tumor suppressor in solid tumors. The oncogenic PI3K pathway suppresses FOXO1 transcriptional activity by enforcing its nuclear exclusion upon AKT-mediated phosphorylation. We show here abundant nuclear expression of FOXO1 in Burkitt lymphoma (BL), a germinal center (GC) B cell derived lymphoma whose pathogenesis is linked to PI3K activation. Recurrent FOXO1 mutations which prevent AKT targeting and lock the transcription factor in the nucleus are used by BL to circumvent mutual exclusivity between PI3K and FOXO1 activation. Using genome editing in human and mouse lymphomas in which MYC and PI3K cooperate synergistically in tumor development we demonstrate pro-proliferative and anti-apoptotic activity of FOXO1 in BL and identify its nuclear localization as an oncogenic event in GC B cell derived lymphomagenesis.
Keywords:B-Lymphocytes, Burkitt Lymphoma, Cell Nucleus, Forkhead Box Protein O1, Gene Editing, Germinal Center, Neoplastic Cell Transformation, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Tumor Cell Line, Animals, Mice
Publisher:American Society of Hematology
Page Range:2670-2683
Date:20 December 2018
Additional Information:Copyright © 2018 by The American Society of Hematology
Official Publication:https://doi.org/10.1182/blood-2018-06-856203
PubMed:View item in PubMed

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