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Updated: Feb 3, 2026

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
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Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches

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Nuclear FOXO1 promotes lymphomagenesis in germinal center B cells

Eleni Kabrani1, Van Trung Chu1,2, Evangelia Tasouri3

  • 1Immune Regulation and Cancer, Max Delbrück Center for Molecular Medicine in the Helmholtz Alliance, Berlin-Buch, Germany.

Blood
|October 19, 2018
PubMed

Insights

Forkhead box class O1 (FOXO1) is typically a tumor suppressor. However, in Burkitt lymphoma, FOXO1 mutations promote cancer by enabling its nuclear localization, driving proliferation and preventing cell death.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Forkhead box class O1 (FOXO1) functions as a tumor suppressor in solid tumors.
  • The phosphoinositide-3-kinase (PI3K) pathway inhibits FOXO1 activity by promoting its nuclear exclusion via AKT-mediated phosphorylation.

Purpose of the Study:

  • To investigate the role of FOXO1 in Burkitt lymphoma (BL), a germinal center (GC) B-cell lymphoma.
  • To understand how BL circumvents the typical tumor-suppressive function of FOXO1 despite PI3K pathway activation.

Main Methods:

  • Analysis of FOXO1 expression in BL samples.
  • Identification and characterization of recurrent FOXO1 mutations in BL.
  • Genome editing in human and mouse lymphoma models with MYC and PI3K cooperation.
  • Assessment of FOXO1's functional impact on proliferation and apoptosis.

Main Results:

  • Abundant nuclear expression of FOXO1 was observed in BL.
  • Recurrent FOXO1 mutations were identified that prevent AKT-mediated phosphorylation, locking FOXO1 in the nucleus.
  • These mutations allow BL to overcome the mutual exclusivity between PI3K and FOXO1 activation.
  • FOXO1 nuclear localization demonstrated proproliferative and antiapoptotic effects in BL models.

Conclusions:

  • FOXO1 nuclear localization is an oncogenic event in GC B-cell-derived lymphomagenesis, specifically in BL.
  • Mutations in FOXO1 are a mechanism by which BL utilizes this transcription factor to promote lymphomagenesis.

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