{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:49:46Z","timestamp":1791308986569,"version":"4.3.1"},"reference-count":149,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015570","name":"Blood Cancer UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015570","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Forkhead box (FOX) class O (FOXO) proteins are a dynamic family of transcription factors composed of four family members: FOXO1, FOXO3, FOXO4 and FOXO6. As context-dependent transcriptional activators and repressors, the FOXO family regulates diverse cellular processes including cell cycle arrest, apoptosis, metabolism, longevity and cell fate determination. A central pathway responsible for negative regulation of FOXO activity is the phosphatidylinositol-3-kinase (PI3K)-AKT signalling pathway, enabling cell survival and proliferation. FOXO family members can be further regulated by distinct kinases, both positively (e.g., JNK, AMPK) and negatively (e.g., ERK-MAPK, CDK2), with additional post-translational modifications further impacting on FOXO activity. Evidence has suggested that FOXOs behave as \u2018\n                    <jats:italic>bona fide<\/jats:italic>\n                    \u2019 tumour suppressors, through transcriptional programmes regulating several cellular behaviours including cell cycle arrest and apoptosis. However, an alternative paradigm has emerged which indicates that FOXOs operate as mediators of cellular homeostasis and\/or resistance in both \u2018normal\u2019 and pathophysiological scenarios. Distinct FOXO family members fulfil discrete roles during normal B cell maturation and function, and it is now clear that FOXOs are aberrantly expressed and mutated in discrete B-cell malignancies. While active FOXO function is generally associated with disease suppression in chronic lymphocytic leukemia for example, FOXO expression is associated with disease progression in diffuse large B cell lymphoma, an observation also seen in other cancers. The opposing functions of the FOXO family drives the debate about the circumstances in which FOXOs favour or hinder disease progression, and whether targeting FOXO-mediated processes would be effective in the treatment of B-cell malignancies. Here, we discuss the disparate roles of FOXO family members in B lineage cells, the regulatory events that influence FOXO function focusing mainly on post-translational modifications, and consider the potential for future development of therapies that target FOXO activity.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2023.1179101","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T03:47:40Z","timestamp":1684381660000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":42,"title":["The discrete roles of individual FOXO transcription factor family members in B-cell malignancies"],"prefix":"10.3389","volume":"14","author":[{"given":"Jamie","family":"Lees","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodie","family":"Hay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Moles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison M.","family":"Michie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2020.11.003","article-title":"Forkhead transcription factors in health and disease","volume":"37","author":"Herman","year":"2021","journal-title":"Trends Genet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1193-230","article-title":"Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma","volume":"5","author":"Galili","year":"1993","journal-title":"Nat Genet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0121474","article-title":"The PAX3-FOXO1 fusion protein present in rhabdomyosarcoma interferes with normal FOXO activity and the TGF-beta pathway","volume":"10","author":"Schmitt-Ney","year":"2015","journal-title":"PloS One"},{"key":"B4","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/sj.onc.1200814","article-title":"Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23)","volume":"14","author":"Borkhardt","year":"1997","journal-title":"Oncogene"},{"key":"B5","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1002\/gcc.2870110203","article-title":"Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family","volume":"11","author":"Parry","year":"1994","journal-title":"Genes Chromosomes Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.9.3714","article-title":"AF6q21, a novel partner of the MLL gene in t (6,11)(q21;q23), defines a forkhead transcriptional factor subfamily","volume":"90","author":"Hillion","year":"1997","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1007\/s10555-020-09883-w","article-title":"FOXO transcription factor family in cancer and metastasis","volume":"39","author":"Jiramongkol","year":"2020","journal-title":"Cancer Metastasis Rev"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2008.06.013","article-title":"Structural basis for DNA recognition by FoxO1 and its regulation by posttranslational modification","volume":"16","author":"Brent","year":"2008","journal-title":"Structure"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1042\/bj3490629","article-title":"Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues","volume":"349","author":"Furuyama","year":"2000","journal-title":"Biochem J"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.24","article-title":"FOXOs, cancer and regulation of apoptosis","volume":"27","author":"Fu","year":"2008","journal-title":"Oncogene"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.21","article-title":"The FoxO code","volume":"27","author":"Calnan","year":"2008","journal-title":"Oncogene"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400093101","article-title":"Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification","volume":"101","author":"Hosaka","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.06.002","article-title":"FoxO transcription factors; regulation by AKT and 14-3-3 proteins","volume":"1813","author":"Tzivion","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.12.029","article-title":"FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis","volume":"128","author":"Paik","year":"2007","journal-title":"Cell"},{"key":"B15","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.semcancer.2017.11.017","article-title":"Re-evaluating the role of FOXOs in cancer","volume":"50","author":"Hornsveld","year":"2018","journal-title":"Semin Cancer Biol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"690","DOI":"10.3324\/haematol.2020.274258","article-title":"Subtype-specific and co-occurring genetic alterations in B-cell non-Hodgkin lymphoma","volume":"107","author":"Ma","year":"2022","journal-title":"Haematologica"},{"key":"B17","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.cell.2017.09.027","article-title":"Genetic and functional drivers of diffuse Large B cell lymphoma","volume":"171","author":"Reddy","year":"2017","journal-title":"Cell"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nature15395","article-title":"Mutations driving CLL and their evolution in progression and relapse","volume":"526","author":"Landau","year":"2015","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0303-x","article-title":"The importance of B cell receptor isotypes and stereotypes in chronic lymphocytic leukemia","volume":"33","author":"Ten Hacken","year":"2019","journal-title":"Leukemia"},{"key":"B20","doi-asserted-by":"publisher","first-page":"208928","DOI":"10.1155\/2014\/208928","article-title":"Does B cell receptor signaling in chronic lymphocytic leukaemia cells differ from that in other B cell types","volume":"2014","author":"Slupsky","year":"2014","journal-title":"Scientifica (Cairo)"},{"key":"B21","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/978-981-15-3532-1_2","article-title":"B cell receptor signaling","volume":"1254","author":"Tanaka","year":"2020","journal-title":"Adv Exp Med Biol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050525","article-title":"FoxO6 transcriptional activity is regulated by Thr26 and Ser184, independent of nucleo-cytoplasmic shuttling","volume":"391","author":"van der Heide","year":"2005","journal-title":"Biochem J"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208063200","article-title":"Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by multiple mechanisms. direct and indirect effects on nuclear\/cytoplasmic shuttling and DNA binding","volume":"277","author":"Zhang","year":"2002","journal-title":"J Biol Chem"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80595-4","article-title":"Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor","volume":"96","author":"Brunet","year":"1999","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80487-0","article-title":"The structural basis for 14-3-3:phosphopeptide binding specificity","volume":"91","author":"Yaffe","year":"1997","journal-title":"Cell"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.002725","article-title":"14-3-3 protein masks the DNA binding interface of forkhead transcription factor FOXO4","volume":"284","author":"Silhan","year":"2009","journal-title":"J Biol Chem"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200112059","article-title":"14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport","volume":"156","author":"Brunet","year":"2002","journal-title":"J Cell Biol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1021\/bi050618r","article-title":"14-3-3 protein interacts with nuclear localization sequence of forkhead transcription factor FoxO4","volume":"44","author":"Obsilova","year":"2005","journal-title":"Biochemistry"},{"key":"B29","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.semcancer.2018.01.004","article-title":"FoxO transcription factors in cancer metabolism","volume":"50","author":"Yadav","year":"2018","journal-title":"Semin Cancer Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.017","article-title":"mTOR signaling in growth control and disease","volume":"149","author":"Laplante","year":"2012","journal-title":"Cell"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.058","article-title":"IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway","volume":"130","author":"Lee","year":"2007","journal-title":"Cell"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1676","article-title":"ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation","volume":"10","author":"Yang","year":"2008","journal-title":"Nat Cell Biol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-4524","article-title":"Activation of FOXO3a is sufficient to reverse mitogen-activated protein\/extracellular signal-regulated kinase kinase inhibitor chemoresistance in human cancer","volume":"70","author":"Yang","year":"2010","journal-title":"Cancer Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1126\/science.1130512","article-title":"CDK2-dependent phosphorylation of FOXO1 as an apoptotic response to DNA damage","volume":"314","author":"Huang","year":"2006","journal-title":"Science"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.9.2263","article-title":"Two novel phosphorylation sites on FKHR that are critical for its nuclear exclusion","volume":"21","author":"Rena","year":"2002","journal-title":"EMBO J"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400048","article-title":"D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a","volume":"5","author":"Rena","year":"2004","journal-title":"EMBO Rep"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600476","article-title":"FOXO transcription factor activation by oxidative stress mediated by the small GTPase ral and JNK","volume":"23","author":"Essers","year":"2004","journal-title":"EMBO J"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12949","article-title":"AMP-activated protein kinase mediates the antioxidant effects of resveratrol through regulation of the transcription factor FoxO1","volume":"281","author":"Yun","year":"2014","journal-title":"FEBS J"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2022.09.010","article-title":"FOXO transcription factors as therapeutic targets in human diseases","volume":"43","author":"Orea-Soufi","year":"2022","journal-title":"Trends Pharmacol Sci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2017.10.006","article-title":"Regulation of FOXO factors in mammalian cells","volume":"127","author":"Brown","year":"2018","journal-title":"Curr Top Dev Biol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094637","article-title":"Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase","volume":"303","author":"Brunet","year":"2004","journal-title":"Science"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100471","article-title":"Methylation by Set9 modulates FoxO3 stability and transcriptional activity","volume":"4","author":"Calnan","year":"2012","journal-title":"Aging (Albany NY)"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.12.4.503","article-title":"Negative regulation of forkhead transcription factor AFX (Foxo4) by CBP-induced acetylation","volume":"12","author":"Fukuoka","year":"2003","journal-title":"Int J Mol Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00126-6","article-title":"Mammalian SIRT1 represses forkhead transcription factors","volume":"116","author":"Motta","year":"2004","journal-title":"Cell"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1469","article-title":"FOXO4 transcriptional activity is regulated by monoubiquitination and USP7\/HAUSP","volume":"8","author":"van der Horst","year":"2006","journal-title":"Nat Cell Biol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.031427","article-title":"Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells","volume":"284","author":"Guttilla","year":"2009","journal-title":"J Biol Chem"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111766108","article-title":"The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor","volume":"108","author":"Welinder","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1891","article-title":"A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate","volume":"11","author":"Lin","year":"2010","journal-title":"Nat Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2017.07.008","article-title":"FOXO in B-cell lymphopoiesis and B cell neoplasia","volume":"50","author":"Ushmorov","year":"2018","journal-title":"Semin Cancer Biol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.01.046","article-title":"B-cell biology and development","volume":"131","author":"Pieper","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1612","article-title":"Foxo1 directly regulates the transcription of recombination-activating genes during B cell development","volume":"9","author":"Amin","year":"2008","journal-title":"Nat Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1667","article-title":"Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation","volume":"9","author":"Dengler","year":"2008","journal-title":"Nat Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2210","article-title":"A self-reinforcing regulatory network triggered by limiting IL-7 activates pre-BCR signaling and differentiation","volume":"13","author":"Ochiai","year":"2012","journal-title":"Nat Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/ni1324","article-title":"A unique function for cyclin D3 in early B cell development","volume":"7","author":"Cooper","year":"2006","journal-title":"Nat Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2011.01.001","article-title":"Emergence of the PI3-kinase pathway as a central modulator of normal and aberrant B cell differentiation","volume":"23","author":"Baracho","year":"2011","journal-title":"Curr Opin Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-331181","article-title":"Pre-B cell receptor-mediated activation of BCL6 induces pre-B cell quiescence through transcriptional repression of MYC","volume":"118","author":"Nahar","year":"2011","journal-title":"Blood"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091299","article-title":"BCL6 is critical for the development of a diverse primary B cell repertoire","volume":"207","author":"Duy","year":"2010","journal-title":"J Exp Med"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxp049","article-title":"Foxo3-\/- mice demonstrate reduced numbers of pre-b and recirculating B cells but normal splenic B cell sub-population distribution","volume":"21","author":"Hinman","year":"2009","journal-title":"Int Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.880668","article-title":"FOXO dictates initiation of B cell development and myeloid restriction in common lymphoid progenitors","volume":"13","author":"Pena-Perez","year":"2022","journal-title":"Front Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.2.740","article-title":"B cell receptor signaling down-regulates forkhead box transcription factor class O 1 mRNA expression via phosphatidylinositol 3-kinase and bruton's tyrosine kinase","volume":"178","author":"Hinman","year":"2007","journal-title":"J Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-09-3071","article-title":"Optimal B-cell proliferation requires phosphoinositide 3-kinase-dependent inactivation of FOXO transcription factors","volume":"104","author":"Yusuf","year":"2004","journal-title":"Blood"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.08.041","article-title":"PI3 kinase signals BCR-dependent mature B cell survival","volume":"139","author":"Srinivasan","year":"2009","journal-title":"Cell"},{"key":"B63","doi-asserted-by":"publisher","first-page":"e2046","DOI":"10.1038\/cddis.2015.396","article-title":"FoxO3 suppresses myc-driven lymphomagenesis","volume":"6","author":"Vandenberg","year":"2016","journal-title":"Cell Death Dis"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-120419-022408","article-title":"Germinal centers","volume":"40","author":"Vicora","year":"2022","journal-title":"Ann Rev Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.10.004","article-title":"T Follicular helper cell differentiation, function, and roles in disease","volume":"41","author":"Crotty","year":"2014","journal-title":"Immunity"},{"key":"B66","doi-asserted-by":"publisher","first-page":"108403","DOI":"10.1016\/j.celrep.2020.108403","article-title":"Cyclin D3 governs clonal expansion of dark zone germinal center B cells","volume":"33","author":"Ramezani-Rad","year":"2020","journal-title":"Cell Rep"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201699","article-title":"Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells","volume":"218","author":"Pae","year":"2021","journal-title":"J Exp Med"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00078-7","article-title":"Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme","volume":"102","author":"Muramatsu","year":"2000","journal-title":"Cell"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00079-9","article-title":"Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the hyper-IgM syndrome (HIGM2)","volume":"102","author":"Revy","year":"2000","journal-title":"Cell"},{"key":"B70","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.immuni.2019.07.001","article-title":"Class-switch recombination occurs infrequently in germinal centers","volume":"51","author":"Roco","year":"2019","journal-title":"Immunity"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2428","article-title":"The proto-oncogene MYC is required for selection in the germinal center and cyclic re-entry","volume":"13","author":"Dominguez-Sola","year":"2012","journal-title":"Nat Immunol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.2.1158","article-title":"Direct repression of prdm1 by bcl-6 inhibits plasmacytic differentiation","volume":"173","author":"Tunyaplin","year":"2014","journal-title":"J Immunol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.10.015","article-title":"The FOXO1 transcription factor instructs the germinal center dark zone program","volume":"43","author":"Dominguez-Sola","year":"2015","journal-title":"Immunity"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.10.021","article-title":"PI3 kinase and FOXO1 transcription factor activity differentially control B cells in the germinal center light and dark zones","volume":"43","author":"Sander","year":"2015","journal-title":"Immunity"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.201900506","article-title":"The AKT isoforms 1 and 2 drive B cell fate decisions during the germinal center response","volume":"2","author":"Zhu","year":"2019","journal-title":"Life Sci Alliance"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161263","article-title":"The transcription factor Foxo1 controls germinal center B cell proliferation in response to T cell help","volume":"214","author":"Inoue","year":"2017","journal-title":"J Exp Med"},{"key":"B77","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.immuni.2018.01.008","article-title":"B cell receptor and CD40 signaling are rewired for synergistic induction of the c-myc transcription factor in germinal center B cells","volume":"48","author":"Luo","year":"2018","journal-title":"Immunity"},{"key":"B78","doi-asserted-by":"publisher","first-page":"107621","DOI":"10.1016\/j.celrep.2020.107621","article-title":"Foxo3 promotes the differentiation and function of follicular helper T cells","volume":"31","author":"Qi","year":"2020","journal-title":"Cell Rep"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.01.003","article-title":"FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress","volume":"128","author":"Tothova","year":"2007","journal-title":"Cell"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/nature08734","article-title":"TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia","volume":"463","author":"Naka","year":"2010","journal-title":"Nature"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1748","article-title":"The antiproliferative activity of kinase inhibitors in chronic myeloid leukemia cells is mediated by FOXO transcription factors","volume":"32","author":"Pellicano","year":"2014","journal-title":"Stem Cells"},{"key":"B82","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.cell.2011.07.032","article-title":"AKT\/FOXO signaling enforces reversible differentiation blockade in myeloid leukemias","volume":"146","author":"Sykes","year":"2011","journal-title":"Cell"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4333","article-title":"Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients","volume":"23","author":"Zehir","year":"2017","journal-title":"Nat Med"},{"key":"B84","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1200\/PO.17.00011","article-title":"OncoKB: a precision oncology knowledge base","author":"Chakravarty","year":"2017","journal-title":"JCO Precis Oncol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-0321","article-title":"Accelerating discovery of functional mutant alleles in cancer","volume":"8","author":"Chang","year":"2018","journal-title":"Cancer Discovery"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1016\/j.immuni.2021.07.009","article-title":"Mutations in the transcription factor FOXO1 mimic positive selection signals to promote germinal center B cell expansion and lymphomagenesis","volume":"54","author":"Roberto","year":"2021","journal-title":"Immunity"},{"key":"B87","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1038\/s41598-022-05334-4","article-title":"FOXO1 forkhead domain mutants in B-cell lymphoma lack transcriptional activity","volume":"12","author":"Sablon","year":"2022","journal-title":"Sci Rep"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.4161\/cc.27727","article-title":"The function of FOXO1 in the late phases of the cell cycle is suppressed by PLK1-mediated phosphorylation","volume":"13","author":"Yuan","year":"2014","journal-title":"Cell Cycle"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M900285-MCP200","article-title":"Global effects of kinase inhibitors on signaling networks revealed by quantitative phosphoproteomics","volume":"8","author":"Pan","year":"2009","journal-title":"Mol Cell Proteomics"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1080\/10428190701817282","article-title":"Characterization of 6q deletions in mature B cell lymphomas and childhood acute lymphoblastic leukemia","volume":"49","author":"Thelander","year":"2008","journal-title":"Leuk Lymphoma"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.7.2157.2157","article-title":"6q deletions define distinct clinico-pathologic subsets of non-hodgkin's lymphoma","volume":"82","author":"Offit","year":"1993","journal-title":"Blood"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07199.x","article-title":"Delineation of distinct tumour profiles in mantle cell lymphoma by detailed cytogenetic, interphase genetic and morphological analysis","volume":"142","author":"Katzenberger","year":"2008","journal-title":"Br J Haematol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.113","article-title":"The pre-B-cell receptor checkpoint in acute lymphoblastic leukaemia","volume":"29","author":"Eswaran","year":"2015","journal-title":"Leukemia"},{"key":"B94","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1111\/imr.12235","article-title":"Mechanisms of pre-B-cell receptor checkpoint control and its oncogenic subversion in acute lymphoblastic leukemia","volume":"263","author":"Buchner","year":"2015","journal-title":"Immunol Rev"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2015.38","article-title":"Genomics in acute lymphoblastic leukaemia: insights and treatment implications","volume":"12","author":"Roberts","year":"2015","journal-title":"Nat Rev Clin Oncol"},{"key":"B96","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3324\/haematol.2014.112912","article-title":"Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia","volume":"100","author":"Safavi","year":"2015","journal-title":"Haematologica"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.9","article-title":"Pre-BCR signaling in precursor B-cell acute lymphoblastic leukemia regulates PI3K\/AKT, FOXO1 and MYC, and can be targeted by SYK inhibition","volume":"30","author":"Kohrer","year":"2016","journal-title":"Leukemia"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1172\/JCI135937","article-title":"DYRK1A regulates B cell acute lymphoblastic leukemia through phosphorylation of FOXO1 and STAT3","volume":"131","author":"Bhansali","year":"2021","journal-title":"J Clin Invest"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-10-813576","article-title":"Tight regulation of FOXO1 is essential for maintenance of B-cell precursor acute lymphoblastic leukemia","volume":"131","author":"Wang","year":"2018","journal-title":"Blood"},{"key":"B100","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41389-021-00377-0","article-title":"CCND3 is indispensable for the maintenance of B-cell acute lymphoblastic leukemia","volume":"11","author":"Ketzer","year":"2022","journal-title":"Oncogenesis"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.007997","article-title":"A conserved phosphorylation site within the forkhead domain of FoxM1B is required for its activation by cyclin-CDK1","volume":"284","author":"Chen","year":"2009","journal-title":"J Biol Chem"},{"key":"B102","doi-asserted-by":"publisher","first-page":"6471","DOI":"10.1038\/ncomms7471","article-title":"Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia","volume":"6","author":"Buchner","year":"2015","journal-title":"Nat Commun"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210519","article-title":"Homeostatic chemokines increase survival of B-chronic lymphocytic leukemia cells through inactivation of transcription factor FOXO3a","volume":"26","author":"Ticchioni","year":"2007","journal-title":"Oncogene"},{"key":"B104","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s12094-012-0922-z","article-title":"Next-generation sequencing reveals the secrets of the chronic lymphocytic leukemia genome","volume":"15","author":"Ramsay","year":"2013","journal-title":"Clin Transl Oncol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.158","article-title":"Activation of the PI3K\/AKT pathway by microRNA-22 results in CLL B-cell proliferation","volume":"29","author":"Palacios","year":"2015","journal-title":"Leukemia"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-2036","article-title":"AKT\/mTORC2 inhibition activates FOXO1 function in CLL cells reducing B-cell receptor-mediated survival","volume":"25","author":"Cosimo","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2018881029","article-title":"IGF1R as druggable target mediating PI3K-delta inhibitor resistance in a murine model of chronic lymphocytic leukemia","volume":"134","author":"Scheffold","year":"2019","journal-title":"Blood"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008101","article-title":"FoxO1-GAB1 axis regulates homing capacity and tonic AKT activity in chronic lymphocytic leukemia","volume":"138","author":"Seda","year":"2021","journal-title":"Blood"},{"key":"B109","doi-asserted-by":"publisher","first-page":"3526","DOI":"10.1038\/s41467-021-23752-2","article-title":"Targeted PI3K\/AKT-hyperactivation induces cell death in chronic lymphocytic leukemia","volume":"12","author":"Ecker","year":"2021","journal-title":"Nat Commun"},{"key":"B110","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1182\/blood.V116.21.772.772","article-title":"Dual inhibition of mTORC1\/mTORC2 induces apoptosis of mantle cell lymphoma by preventing rictor mediated AKTS473 phosphorylation by potentiating AKT2-PHLPP1 association","volume":"116","author":"Gupta","year":"2010","journal-title":"Blood"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1172\/JCI160767","article-title":"A FOXO1-dependent transcription network is a targetable vulnerability of mantle cell lymphomas","volume":"132","author":"Jang","year":"2022","journal-title":"J Clin Invest"},{"key":"B112","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1053\/j.seminoncol.2018.07.005","article-title":"New concepts in follicular lymphoma biology: from BCL2 to epigenetic regulators and non-coding RNAs","volume":"45","author":"Devan","year":"2018","journal-title":"Semin Oncol"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-01-479865","article-title":"Analysis of FOXO1 mutations in diffuse large B-cell lymphoma","volume":"121","author":"Trinh","year":"2013","journal-title":"Blood"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-06-856203","article-title":"Nuclear FOXO1 promotes lymphomagenesis in germinal center B cells","volume":"132","author":"Kabrani","year":"2018","journal-title":"Blood"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00169-2","article-title":"Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry","volume":"16","author":"Pastore","year":"2015","journal-title":"Lancet Oncol"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12132","article-title":"Acquired resistance to venetoclax (ABT-199) in t(14;18) positive lymphoma cells","volume":"7","author":"Bodo","year":"2016","journal-title":"Oncotarget"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1038\/nature11378","article-title":"Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics","volume":"490","author":"Schmitz","year":"2012","journal-title":"Nature"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1101\/gad.453107","article-title":"FoxO transcription factors suppress myc-driven lymphomagenesis via direct activation of arf","volume":"21","author":"Bouchard","year":"2007","journal-title":"Genes Dev"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018029546","article-title":"Sporadic and endemic Burkitt lymphoma have frequent FOXO1 mutations but distinct hotspots in the AKT recognition motif","volume":"3","author":"Zhou","year":"2019","journal-title":"Blood Adv"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.008649","article-title":"AMPK and AKT protein kinases hierarchically phosphorylate the N-terminus of the FOXO1 transcription factor, modulating interactions with 14-3-3 proteins","volume":"294","author":"Saline","year":"2019","journal-title":"J Biol Chem"},{"key":"B121","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.3390\/cancers11101427","article-title":"FOXO1 confers maintenance of the dark zone proliferation and survival program and can be pharmacologically targeted in Burkitt lymphoma","volume":"11","author":"Gehringer","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012914","article-title":"The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma","volume":"346","author":"Rosenwald","year":"2002","journal-title":"N Engl J Med"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0016-8","article-title":"Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes","volume":"24","author":"Chapuy","year":"2018","journal-title":"Nat Med"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2123","article-title":"Genetic landscapes of relapsed and refractory diffuse Large B-cell lymphomas","volume":"22","author":"Morin","year":"2016","journal-title":"Clin Cancer Res"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-11-764332","article-title":"Genetics of diffuse large B-cell lymphoma","volume":"131","author":"Pasqualucci","year":"2018","journal-title":"Blood"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1423183","article-title":"FOXO1 promotes resistance of non-Hodgkin lymphomas to anti-CD20-based therapy","volume":"7","author":"Pyrzynska","year":"2018","journal-title":"Oncoimmunology"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200112876","article-title":"The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression","volume":"108","author":"Nakae","year":"2001","journal-title":"J Clin Invest"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00401-X","article-title":"The forkhead transcription factor Foxo1 regulates adipocyte differentiation","volume":"4","author":"Nakae","year":"2003","journal-title":"Dev Cell"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-06-654111","article-title":"FOXO1 activation is an effector of SYK and AKT inhibition in tonic BCR signal-dependent diffuse large B-cell lymphomas","volume":"127","author":"Szydlowski","year":"2016","journal-title":"Blood"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13690","article-title":"FOXO4 expression is related to stem cell-like properties and resistance to treatment in diffuse large B-cell lymphoma","volume":"8","author":"Ryu","year":"2017","journal-title":"Oncotarget"},{"key":"B131","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1038\/s41419-019-2158-0","article-title":"Resistance to BTK inhibition by ibrutinib can be overcome by preventing FOXO3a nuclear export and PI3K\/AKT activation in B-cell lymphoid malignancies","volume":"10","author":"Kapoor","year":"2019","journal-title":"Cell Death Dis"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.4084\/mjhid.2020.073","article-title":"Proliferation and apoptosis of B-cell lymphoma cells under targeted regulation of FOXO3 by miR-155","volume":"12","author":"Zheng","year":"2020","journal-title":"Mediterr J Hematol Infect Dis"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-381905","article-title":"FOXO1 is a tumor suppressor in classical Hodgkin lymphoma","volume":"119","author":"Xie","year":"2012","journal-title":"Blood"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-07-795278","article-title":"Fine-tuning of FOXO3A in cHL as a survival mechanism and a hallmark of abortive plasma cell differentiation","volume":"131","author":"Osswald","year":"2018","journal-title":"Blood"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2189","article-title":"Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets","volume":"7","author":"Hideshima","year":"2007","journal-title":"Nat Rev Cancer"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1080\/10428190802304966","article-title":"Growth control of multiple myeloma cells through inhibition of glycogen synthase kinase-3","volume":"49","author":"Zhou","year":"2008","journal-title":"Leuk Lymphoma"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14207","article-title":"Akt inhibition synergizes with polycomb repressive complex 2 inhibition in the treatment of multiple myeloma","volume":"110","author":"Rizk","year":"2019","journal-title":"Cancer Sci"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019001393","article-title":"AKT signaling restrains tumor suppressive functions of FOXO transcription factors and GSK3 kinase in multiple myeloma","volume":"4","author":"Bloedjes","year":"2020","journal-title":"Blood Adv"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-232801","article-title":"IGF-1 suppresses bim expression in multiple myeloma via epigenetic and posttranslational mechanisms","volume":"115","author":"De Bruyne","year":"2010","journal-title":"Blood"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.594","article-title":"The PI3K inhibitor GDC-0941 combines with existing clinical regimens for superior activity in multiple myeloma","volume":"33","author":"Munugalavadla","year":"2014","journal-title":"Oncogene"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-0605","article-title":"Proteasome inhibition causes regression of leukemia and abrogates BCR-ABL-induced evasion of apoptosis in part through regulation of forkhead tumor suppressors","volume":"69","author":"Jagani","year":"2009","journal-title":"Cancer Res"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(20)30120-4","article-title":"Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial","volume":"7","author":"Kalakonda","year":"2020","journal-title":"Lancet Haematol"},{"key":"B143","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.bcp.2017.11.009","article-title":"FoxO-1 contributes to the efficacy of the combination of the XPO1 inhibitor selinexor and cisplatin in ovarian carcinoma preclinical models","volume":"147","author":"Corno","year":"2018","journal-title":"Biochem Pharmacol"},{"key":"B144","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.canlet.2021.01.008","article-title":"XPO1 inhibition synergizes with PARP1 inhibition in small cell lung cancer by targeting nuclear transport of FOXO3a","volume":"503","author":"Wang","year":"2021","journal-title":"Cancer Lett"},{"key":"B145","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1038\/nm.2772","article-title":"Beta-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer","volume":"18","author":"Tenbaum","year":"2012","journal-title":"Nat Med"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.355","article-title":"FOXO3 expression during colorectal cancer progression: biomarker potential reflects a tumour suppressor role","volume":"109","author":"Bullock","year":"2013","journal-title":"Br J Cancer"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2603","article-title":"FOXO1 inhibits Runx2 transcriptional activity and prostate cancer cell migration and invasion","volume":"71","author":"Zhang","year":"2011","journal-title":"Cancer Res"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2012-704","article-title":"Expression of FOXO1 is associated with GATA3 and annexin-1 and predicts disease-free survival in breast cancer","volume":"2","author":"Wu","year":"2012","journal-title":"Am J Cancer Res"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08951.x","article-title":"The tumour suppressor FOXO3 is a key regulator of mantle cell lymphoma proliferation and survival","volume":"156","author":"Obrador-Hevia","year":"2012","journal-title":"Br J Haematol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1179101\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T03:47:44Z","timestamp":1684381664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1179101\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,18]]},"references-count":149,"alternative-id":["10.3389\/fimmu.2023.1179101"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1179101","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,18]]},"article-number":"1179101"}}