FOXO in B-cell lymphopoiesis and B cell neoplasia.

FOX O family transcription factors are important for differentiation and function of multiple cell types. In B lymphocytes they play a critical role. The activity of FOXOs is directly regulated both by signaling from B cell receptor (BCR) and cytokine receptors. FOXO1 action controls the transition between differentiation stages of B cell development. In comparison to other FOXO family members, FOXO1 plays a superior role in the regulation of early stages of B-cell differentiation. Although being known as a negative regulator of cell proliferation and therefore potential tumor suppressor, FOXO1 is downregulated only in Hodgkin lymphoma (HL) subtypes. In non-Hodgkin lymphoma (NHL) entities its expression is maintained at significant levels, raising the question on the role of FOXO-transcription factors in the proliferation and survival programs in the process of B cell differentiation as well as their contribution to the oncogenic programs of B-cell lymphomas. In particular, we discuss molecular mechanisms that might determine the switch between pro-apoptotic and pro-survival effects of FOXO1 and their interplay with specific differentiation programs.

• Publication year

  2017

• Venue

  Seminars in Cancer Biology

• Publication date

  2017-07-31

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.semcancer.2017.07.008PMID 28774833
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• AKT/PKB Signaling: Navigating the Network.

  2017cited by this paper
• NF-κB–driven suppression of FOXO3a contributes to EGFR mutation-independent gefitinib resistance

  2016cited by this paper
• Pre-BCR signaling in precursor B-cell acute lymphoblastic leukemia regulates PI3K/AKT, FOXO1 and MYC, and can be targeted by SYK inhibition

  2016cited by this paper
• FoxO3a confers cetuximab resistance in RAS wild-type metastatic colorectal cancer through c-Myc

  2016cited by this paper
• FOXO4 expression is related to stem cell-like properties and resistance to treatment in diffuse large B-cell lymphoma

  2016cited by this paper
• FoxO1 Plays an Important Role in Regulating β-Cell Compensation for Insulin Resistance in Male Mice.

  2016cited by this paper
• PTEN opposes negative selection and enables oncogenic transformation of pre-B cells

  2016cited by this paper
• Hodgkin lymphoma: Pathology and biology.

  2016cited by this paper
• FOXO1 activation is an effector of SYK and AKT inhibition in tonic BCR signal-dependent diffuse large B-cell lymphomas.

  2016cited by this paper
• FOXO transcription factors in cancer development and therapy

  2016cited by this paper
• Differential regulation of mTOR signaling determines sensitivity to AKT inhibition in diffuse large B cell lymphoma

  2016cited by this paper
• The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia

  2016cited by this paper
• FoxO3 suppresses Myc-driven lymphomagenesis

  2016cited by this paper
• Genetic Landscapes of Relapsed and Refractory Diffuse Large B-Cell Lymphomas

  2015cited by this paper
• Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia.

  2015cited by this paper
• DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control

  2015cited by this paper
• Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia

  2015cited by this paper
• PI3 Kinase and FOXO1 Transcription Factor Activity Differentially Control B Cells in the Germinal Center Light and Dark Zones.

  2015cited by this paper
• Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia

  2015cited by this paper
• NF-κB and AKT signaling prevent DNA damage in transformed pre-B cells by suppressing RAG1/2 expression and activity.

  2015cited by this paper
• The forkhead transcription factor FOXP1 represses human plasma cell differentiation.

  2015cited by this paper
• Low expression of pro-apoptotic Bcl-2 family proteins sets the apoptotic threshold in Waldenström Macroglobulinemia

  2015cited by this paper
• Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia

  2015cited by this paper
• Transcription factor networks in B-cell differentiation link development to acute lymphoid leukemia.

  2015cited by this paper
• Whole-exome analysis reveals novel somatic genomic alterations associated with outcome in immunochemotherapy-treated diffuse large B-cell lymphoma

  2015cited by this paper
• Dynamics of B cells in germinal centres

  2015cited by this paper
• Mechanisms of pre‐B‐cell receptor checkpoint control and its oncogenic subversion in acute lymphoblastic leukemia

  2015cited by this paper
• Genomics in acute lymphoblastic leukaemia: insights and treatment implications

  2015cited by this paper
• Evaluation of AKT phosphorylation and PTEN loss and their correlation with the resistance of rituximab in DLBCL.

  2015cited by this paper
• Self-enforcing feedback activation between BCL6 and pre-B cell receptor signaling defines a distinct subtype of acute lymphoblastic leukemia.

  2015cited by this paper
• The pre-B-cell receptor checkpoint in acute lymphoblastic leukaemia

  2015cited by this paper
• The FOXO1 Transcription Factor Instructs the Germinal Center Dark Zone Program.

  2015cited by this paper
• FOXO3a and Posttranslational Modifications Mediate Glucocorticoid Sensitivity in B-ALL

  2015cited by this paper
• Absence of manganese superoxide dismutase delays p53-induced tumor formation

  2014cited by this paper
• CDK4 deficiency promotes genomic instability and enhances Myc-driven lymphomagenesis.

  2014cited by this paper
• FOXO1 repression contributes to block of plasma cell differentiation in classical Hodgkin lymphoma.

  2014cited by this paper
• Promiscuous Rearrangements of the MYC Locus Hijack Enhancers and Super-Enhancers to Dysregulate MYC Expression in Multiple Myeloma

  2014cited by this paper
• FOXO1 downregulation contributes to the oncogenic program of primary mediastinal B-cell lymphoma

  2014cited by this paper
• Analysis of Cell Cycle , Thymidine Uptake , Modified Boyden Chamber , and Scratch Wound Assays

  2014cited by this paper
• FOXO1-Mediated Activation of Akt Plays a Critical Role in Vascular Homeostasis

  2014cited by this paper
• PI3Kδ Inhibition Augments the Efficacy of Rapamycin in Suppressing Proliferation of Epstein−Barr Virus (EBV)+ B Cell Lymphomas

  2013cited by this paper
• Integrated genetic and epigenetic analysis of childhood acute lymphoblastic leukemia.

  2013cited by this paper
• The Paradox of Akt-mTOR Interactions

  2013cited by this paper
• Foxo‐mediated Bim transcription is dispensable for the apoptosis of hematopoietic cells that is mediated by this BH3‐only protein

  2013cited by this paper
• Analysis of FOXO1 mutations in diffuse large B-cell lymphoma.

  2013cited by this paper
• mTOR complex 2 controls glycolytic metabolism in glioblastoma through FoxO acetylation and upregulation of c-Myc.

  2013cited by this paper
• Using biologic predictive factors to direct therapy of diffuse large B-cell lymphoma

  2013cited by this paper
• STAT5 Outcompetes STAT3 To Regulate the Expression of the Oncogenic Transcriptional Modulator BCL6

  2013cited by this paper
• B-cell biology and development.

  2013cited by this paper
• A Replicative Self-Renewal Model for Long-Lived Plasma Cells: Questioning Irreversible Cell Cycle Exit

  2013cited by this paper
• New insights into pre-BCR and BCR signalling with relevance to B cell malignancies

  2013cited by this paper
• FOXP1 acts through a negative feedback loop to suppress FOXO-induced apoptosis

  2013cited by this paper
• FOXOs: signalling integrators for homeostasis maintenance

  2013cited by this paper
• Downregulation of FOXP1 is required during germinal center B-cell function.

  2013cited by this paper
• PTEN loss defines a PI3K/AKT pathway-dependent germinal center subtype of diffuse large B-cell lymphoma

  2013cited by this paper
• PDK1 regulates VDJ recombination, cell-cycle exit and survival during B-cell development

  2013cited by this paper
• Expression of FoxO3a in clinical cases of malignant lymphoma.

  2013cited by this paper
• Lymphocyte signaling: regulation of FoxO transcription factors by microRNAs

  2012cited by this paper
• Molecular genetics of B-precursor acute lymphoblastic leukemia.

  2012cited by this paper
• Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate

  2012cited by this paper
• FOXO transcription factors throughout T cell biology

  2012cited by this paper
• Synergy between PI3K signaling and MYC in Burkitt lymphomagenesis.

  2012cited by this paper
• Gene expression profiling of microdissected Hodgkin Reed-Sternberg cells correlates with treatment outcome in classical Hodgkin lymphoma.

  2012cited by this paper
• FOXO1 is a tumor suppressor in classical Hodgkin lymphoma.

  2012cited by this paper
• In Vitro Generation of Long-lived Human Plasma Cells

  2012cited by this paper
• Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics

  2012cited by this paper
• mTOR signaling in growth control and disease.

  2012cited by this paper
• Regulation of cell cycle progression by forkhead transcription factor FOXO3 through its binding partner DNA replication factor Cdt1

  2012cited by this paper
• Forkhead Transcription Factor FOXO3a Protein Activates Nuclear Factor κB through B-cell lymphoma/leukemia 10 (BCL10) Protein and Promotes Tumor Cell Survival in Serum Deprivation*

  2012cited by this paper
• A self-reinforcing regulatory network triggered by limiting IL-7 activates pre-BCR signaling and differentiation

  2012cited by this paper
• Epstein-Barr virus exploits intrinsic B-lymphocyte transcription programs to achieve immortal cell growth

  2011cited by this paper
• The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor

  2011cited by this paper
• Pre-B cell receptor-mediated activation of BCL6 induces pre-B cell quiescence through transcriptional repression of MYC.

  2011cited by this paper
• Regulation of glucose homeostasis through a XBP-1–FoxO1 interaction

  2011cited by this paper
• Interplay between FOXO, TOR, and Akt.

  2011cited by this paper
• Abstract LB-235: BCL6 enables Ph+ acute lymphoblastic leukemia cells to survive BCR-ABL1 kinase inhibition

  2011cited by this paper
• Frequent mutation of histone modifying genes in non-Hodgkin lymphoma

  2011cited by this paper
• Membrane-associated signaling in human B-lymphoma lines.

  2011cited by this paper
• Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors

  2011cited by this paper
• BCL6 enables Ph+ acute lymphoblastic leukemia cells to survive BCR-ABL1 kinase inhibition

  2011cited by this paper
• Role of PI3K in the generation and survival of B cells

  2010cited by this paper
• The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes

  2010cited by this paper
• Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma

  2010cited by this paper
• IGF-1 suppresses Bim expression in multiple myeloma via epigenetic and posttranslational mechanisms.

  2010cited by this paper
• FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and Rictor.

  2010cited by this paper
• Stem Cells , Tissue Engineering and Hematopoietic Elements Tumorigenic Potential of Mononucleated Small Cells of Hodgkin Lymphoma Cell Lines

  2010cited by this paper
• A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates the B cell fate

  2010cited by this paper
• Tumorigenic potential of mononucleated small cells of Hodgkin lymphoma cell lines.

  2010cited by this paper
• Integrated Genetic and Epigenetic Analysis of Childhood Acute Lymphoblastic Leukemia Reveals a Synergistic Role for Structural and Epigenetic Lesions In Determining Disease Phenotype

  2010cited by this paper
• IRF4: Immunity. Malignancy! Therapy?

  2009cited by this paper
• PI3 kinase signals BCR-dependent mature B cell survival.

  2009cited by this paper
• The Transcription of FOXO Genes Is Stimulated by FOXO3 and Repressed by Growth Factors*

  2009cited by this paper
• BCL6 is critical for the development of a diverse primary B cell repertoire

  2009cited by this paper
• Increased AKT S473 phosphorylation after mTORC1 inhibition is rictor dependent and does not predict tumor cell response to PI3K/mTOR inhibition

  2009cited by this paper
• Coordinate Regulation of FOXO1 by miR-27a, miR-96, and miR-182 in Breast Cancer Cells

  2009cited by this paper
• The IKK2/NF-{kappa}B pathway suppresses MYC-induced lymphomagenesis.

  2009cited by this paper
• Characterization of 6q deletions in mature B cell lymphomas and childhood acute lymphoblastic leukemia

  2008cited by this paper
• The FoxO code

  2008cited by this paper
• A brief introduction to FOXOlogy

  2008cited by this paper
• Distinct roles for Foxo1 at multiple stages of B cell differentiation

  2008cited by this paper

• 20-hydroxyecdysone promotes brain development via upregulating MMP2 expression during metamorphosis in Helicoverpa armigera

  2026cites this paper
• Ex vivo modelling reveals low levels of CKS1 inhibition boost haematopoiesis via AKT/Foxo1 signalling.

  2025cites this paper
• Beyond FOXO1: AS1842856 inhibits GSK3 to enhance cytotoxic effects in B-ALL

  2025cites this paper
• Biphasic control of the B cell transcriptome by mTORC1 and GSK3

  2025cites this paper
• FoxO1 signaling in B cell malignancies and its therapeutic targeting

  2024cites this paper
• UPF1 regulates FOXO1 protein expression by promoting PBK transcription in non-small cell lung cancer.

  2023cites this paper
• The discrete roles of individual FOXO transcription factor family members in B-cell malignancies

  2023cites this paper
• Disruption to the FOXO-PRDM1 axis resulting from deletions of chromosome 6 in acute lymphoblastic leukaemia

  2023cites this paper
• Decreased FOXO1 Expression Is Correlated with Poor Prognosis in Myelodysplastic Syndromes

  2022cites this paper
• Altered pathways and targeted therapy in double hit lymphoma

  2022cites this paper
• Protein Arginine Methylation: An Emerging Modification in Cancer Immunity and Immunotherapy

  2022cites this paper
• Oncogenic mutations in the DNA-binding domain of FOXO1 disrupt folding: quantitative insights from experiments and molecular simulations

  2022cites this paper
• Identification of Critical Genes and Signaling Pathways in Human Monocytes Following High-Intensity Exercise

  2021cites this paper
• B Cell Receptor-Responsive miR-141 Enhances Epstein-Barr Virus Lytic Cycle via FOXO3 Inhibition

  2021cites this paper
• Decitabine Induces Change of Biological Traits in Myelodysplastic Syndromes via FOXO1 Activation

  2020cites this paper
• FOXF2 acts as a crucial molecule in tumours and embryonic development

  2020cites this paper
• Distinctive Tissue and Serum MicroRNA Profile of IgG4-Related Ophthalmic Disease and MALT Lymphoma

  2020cites this paper
• AKT signaling restrains tumor suppressive functions of FOXO transcription factors and GSK3 kinase in multiple myeloma.

  2020cites this paper
• Down-Regulated FOXO1 in Refractory/Relapse Childhood B-Cell Acute Lymphoblastic Leukemia

  2020cites this paper
• Proliferation and Apoptosis of B-Cell Lymphoma Cells under Targeted Regulation of FOXO3 by miR-155

  2020cites this paper
• Characterization of rare germline variants in familial multiple myeloma

  2020cites this paper
• Sporadic and endemic Burkitt lymphoma have frequent FOXO1 mutations but distinct hotspots in the AKT recognition motif.

  2019cites this paper
• Recent Advances in Understanding FOXN3 in Breast Cancer, and Other Malignancies

  2019cites this paper
• B Cell Receptor-Responsive miR-141 and viral miR-BART9 promote Epstein-Barr Virus Reactivation Through FOXO3 Inhibition

  2019cites this paper
• Depletion of the transcriptional coactivators CREB-binding protein or EP300 downregulates CD20 in diffuse large B-cell lymphoma cells and impairs the cytotoxic effects of anti-CD20 antibodies.

  2019cites this paper
• FoxO1 controls the expansion of pre-B cells by regulating the expression of interleukin 7 receptor α chain and its signal pathway.

  2019cites this paper
• Tight regulation of FOXO1 is essential for maintenance of B-cell precursor acute lymphoblastic leukemia.

  2018cites this paper
• Imaging flow cytometry: A method for examining dynamic native FOXO1 localization in human lymphocytes.

  2018cites this paper
• Nuclear Fox(O1): not so fantastic.

  2018cites this paper
• Systems analysis of key genes and pathways in the progression of hepatocellular carcinoma

  2018cites this paper
• EDITORIAL.

  2018cites this paper