{"id":"https://openalex.org/W3016981580","doi":"https://doi.org/10.1182/blood.v104.11.2366.2366","title":"Arsenic Trioxide (ATO) Induced Apoptosis in Myelodysplastic Syndrome (MDS): The Role of TNFa and NFkB.","display_name":"Arsenic Trioxide (ATO) Induced Apoptosis in Myelodysplastic Syndrome (MDS): The Role of TNFa and NFkB.","publication_year":2004,"publication_date":"2004-11-16","ids":{"openalex":"https://openalex.org/W3016981580","doi":"https://doi.org/10.1182/blood.v104.11.2366.2366","mag":"3016981580"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v104.11.2366.2366","doi":"https://doi.org/10.1182/blood.v104.11.2366.2366","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v104.11.2366.2366","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5110548304","display_name":"Daniella M. Bahia Kerbauy","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"D.M. B. Kerbauy","raw_affiliation_strings":["Clinical Research Division, Fred Hutchinson Cancer Research Center"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Clinical Research Division, Fred Hutchinson Cancer Research Center","institution_ids":["https://openalex.org/I4210089486"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074629157","display_name":"Bart Lee Scott","orcid":"https://orcid.org/0000-0001-9620-7839","observed_orcids":["https://orcid.org/0000-0001-9620-7839"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]},{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"B. Scott","raw_affiliation_strings":["Clinical Research Division, Fred Hutchinson Cancer Research Center","University of Washington, Seattle, WA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Clinical Research Division, Fred Hutchinson Cancer Research Center","institution_ids":["https://openalex.org/I4210089486"]},{"raw_affiliation_string":"University of Washington, Seattle, WA, USA","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5054653166","display_name":"Sudeshna Seal","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"S. Seal","raw_affiliation_strings":["Clinical Research Division, Fred Hutchinson Cancer Research Center"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Clinical Research Division, Fred Hutchinson Cancer Research Center","institution_ids":["https://openalex.org/I4210089486"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056473479","display_name":"Nissa Abbasi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"N. Abbasi","raw_affiliation_strings":["Clinical Research Division, Fred Hutchinson Cancer Research Center"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Clinical Research Division, Fred Hutchinson Cancer Research Center","institution_ids":["https://openalex.org/I4210089486"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5010962133","display_name":"H. Joachim Deeg","orcid":"https://orcid.org/0000-0002-4426-9023","observed_orcids":["https://orcid.org/0000-0002-4426-9023"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]},{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"H. Joachim Deeg","raw_affiliation_strings":["Clinical Research Division, Fred Hutchinson Cancer Research Center","University of Washington, Seattle, WA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Clinical Research Division, Fred Hutchinson Cancer Research Center","institution_ids":["https://openalex.org/I4210089486"]},{"raw_affiliation_string":"University of Washington, Seattle, WA, USA","institution_ids":["https://openalex.org/I201448701"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":{"value":0.29611131,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"104","issue":"11","first_page":"2366","last_page":"2366"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11559","display_name":"Retinoids in leukemia and cellular processes","score":0.6054999828338623,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11559","display_name":"Retinoids in leukemia and cellular processes","score":0.6054999828338623,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.3091000020503998,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11591","display_name":"NF-\u03baB Signaling Pathways","score":0.030500000342726707,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/arsenic-trioxide","display_name":"arsenic trioxide","score":0.9980000257492065},{"id":"https://openalex.org/keywords/myelodysplastic-syndrome","display_name":"myelodysplastic syndrome","score":0.996999979019165},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.9729999899864197},{"id":"https://openalex.org/keywords/nf-kappab-activation","display_name":"NF-\u03baB activation","score":0.7620000243186951},{"id":"https://openalex.org/keywords/tnf-alpha","display_name":"TNF-\u03b1","score":0.8899999856948853},{"id":"https://openalex.org/keywords/ikappabalpha-phosphorylation","display_name":"I\u03baB\u03b1 phosphorylation","score":0.7799999713897705},{"id":"https://openalex.org/keywords/flip","display_name":"c-FLIP","score":0.8019999861717224},{"id":"https://openalex.org/keywords/tnf-receptor-signaling","display_name":"TNF receptor signaling","score":0.5590000152587891},{"id":"https://openalex.org/keywords/cd34-cells","display_name":"CD34+ cells","score":0.7260000109672546},{"id":"https://openalex.org/keywords/hematopoietic-stem-cells","display_name":"hematopoietic stem cells","score":0.5770000219345093},{"id":"https://openalex.org/keywords/etanercept","display_name":"etanercept","score":0.3160000145435333}],"concepts":[{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.6957314610481262},{"id":"https://openalex.org/C88634738","wikidata":"https://www.wikidata.org/wiki/Q24769543","display_name":"Annexin","level":3,"score":0.5818148255348206},{"id":"https://openalex.org/C17991360","wikidata":"https://www.wikidata.org/wiki/Q21173843","display_name":"Tumor necrosis factor alpha","level":2,"score":0.5803659558296204},{"id":"https://openalex.org/C2775934118","wikidata":"https://www.wikidata.org/wiki/Q424169","display_name":"Propidium iodide","level":4,"score":0.5757983922958374},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5340157151222229},{"id":"https://openalex.org/C2780386689","wikidata":"https://www.wikidata.org/wiki/Q7739","display_name":"Arsenic trioxide","level":3,"score":0.528401255607605},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.48675107955932617},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.3605473041534424},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3581838011741638},{"id":"https://openalex.org/C31573885","wikidata":"https://www.wikidata.org/wiki/Q304484","display_name":"Programmed cell death","level":3,"score":0.2515074610710144},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.06729996204376221}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v104.11.2366.2366","doi":"https://doi.org/10.1182/blood.v104.11.2366.2366","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v104.11.2366.2366","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":1.0}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2011140047","https://openalex.org/W4417333643","https://openalex.org/W1989021153","https://openalex.org/W2143013835","https://openalex.org/W2890149960","https://openalex.org/W2019619526","https://openalex.org/W2379480262","https://openalex.org/W1970343951","https://openalex.org/W2351985543","https://openalex.org/W2072430692"],"abstract_inverted_index":{"Abstract":[0],"The":[1,133,469,480],"mechanism":[2,464],"by":[3,39,97,144,501],"which":[4,246],"ATO":[5,32,53,106,136,169,256,306,330,388,412,414,433,445,449,487],"induces":[6,33],"hematologic":[7],"responses":[8],"in":[9,51,66,83,118,120,129,197,206,213,263,272,309,312,321,335,341,347,356,376,382,385,396,404,417,426,446,494],"patients":[10,125,233,495],"with":[11,41,105,126,234,255,411,472,496],"MDS":[12,89,268,314,360,408,447,497],"is":[13,49],"not":[14,288,373],"well":[15],"defined,":[16],"and":[17,62,90,100,113,128,137,146,165,172,181,228,266,286,311,337,358,367,406,444,450,488],"a":[18,45,109,317,377,392],"better":[19],"understanding":[20],"might":[21],"help":[22],"to":[23,57,63,79,199,208,217,243,251,281,316,329,387,430,466],"optimize":[24],"the":[25,158,273,418,457,462],"efficacy":[26],"of":[27,37,135,148,160,186,225,260,275,304,326,369,380,394,420,424,442,459,486],"ATO.":[28],"Among":[29],"other":[30],"effects":[31],"apoptosis":[34,65,171,308,334,344,381],"via":[35],"inhibition":[36,141,262,292],"NFkB":[38,47,60,81,140,173,240,284,291,354],"interfering":[40],"IkB":[42],"kinases.":[43],"TNFa,":[44,390],"potent":[46],"stimulus,":[48],"upregulated":[50],"MDS.":[52],"has":[54],"been":[55],"shown":[56],"prevent":[58,282],"TNFa-induced":[59],"activation,":[61,285],"induce":[64],"various":[67],"neoplastic":[68],"cells.":[69,131,448],"Methods:":[70],"1)":[71],"We":[72],"used":[73],"eletrophoretic":[74],"mobility":[75],"shift":[76],"assays":[77],"(EMSA)":[78],"determine":[80],"activation":[82,174,241,355],"marrow":[84],"mononuclear":[85],"cells":[86,215,230,315,332,339,349,361,384,409,428,505],"(MMC)":[87],"from":[88,122,223,231],"normal":[91,252,322,348,508],"marrows.":[92],"2)":[93],"Apoptosis":[94,205],"was":[95,142,150,210,345,362],"determined":[96,151,176,196,212],"Annexin":[98],"V":[99],"propidium":[101],"iodide":[102],"following":[103],"treatments":[104],"(2-200uM),":[107],"Enbrel,":[108],"soluble":[110],"TNF-receptor":[111],"(5ug/ml),":[112],"TNFa":[114,161,443],"(20ng/ml),":[115],"alone":[116],"or":[117],"combination,":[119],"marrows":[121],"healthy":[123],"donors,":[124],"MDS,":[127],"ML1":[130,214,265,310,336,357,383,405,427],"3)":[132],"effect":[134],"Enbrel":[138,279,473,489],"on":[139],"evaluated":[143],"EMSA,":[145],"phosphorylation":[147],"IKB\u03b1":[149],"using":[152,201],"western":[153],"blots.":[154],"4)":[155],"To":[156],"define":[157],"role":[159,393],"receptor":[162],"(R)":[163],"1":[164,180,371],"2":[166,182],"signaling":[167],"for":[168,297],"activity,":[170],"were":[175,195,301,401],"while":[177,506],"blocking":[178,368],"TNFR":[179,365,370],"respectively.":[183],"5)":[184],"Levels":[185],"FLIP,":[187],"an":[188],"NFkB-dependent":[189],"gene":[190],"that":[191,475,484],"modulates":[192],"death":[193],"signaling,":[194],"response":[198,207,386],"treatment":[200],"real-time":[202],"PCR.":[203],"6)":[204],"ATO/TNF/Enbrel":[209],"also":[211,482],"transduced":[216],"overexpress":[218],"FLIP":[219,399],"long.":[220],"Results:":[221],"MMC":[222],"7":[224],"8":[226],"patients,":[227],"CD34+":[229],"all":[232],"RAEB":[235,338],"tested":[236],"showed":[237,247],"high":[238],"constitutive":[239],"(compared":[242],"RA/RARS":[244],"marrows,":[245],"low":[248],"activity":[249],"comparable":[250],"marrows).":[253],"Treatment":[254],"induced":[257,307,353,434],"similar":[258],"patterns":[259,303],"NF\u03baB":[261],"normal,":[264],"primary":[267,313,359,407],"(RAEB)":[269],"cells,":[270],"even":[271],"presence":[274,419],"exogenous":[276,421],"TNFa.":[277],"Interestingly,":[278],"failed":[280,429],"TNF-induced":[283],"did":[287],"enhance":[289],"ATO-induced":[290,397],"(Figure":[293,350],"B:":[294],"EMSA;Western":[295],"blot":[296],"P-IKB).":[298],"However,":[299],"there":[300],"distinct":[302],"apoptosis:":[305],"greater":[318],"extent":[319],"than":[320],"controls.":[323],"While":[324],"addition":[325],"(exogenous)":[327],"TNF":[328],"treated":[331,410],"enhanced":[333],"(less":[340],"RA":[342],"marrow),":[343],"decreased":[346],"A).":[351],"TNF-a":[352,451],"mediated":[363],"through":[364],"1,":[366],"(but":[372],"TNFR2)":[374],"resulted":[375],"significant":[378],"reduction":[379],"+":[389],"suggesting":[391],"TNF-\u03b1/TNFR1":[395],"apoptosis.":[398,435],"levels":[400],"down":[402],"regulated":[403],"(or":[413],"plus":[415],"Enbrel)":[416],"TNF;":[422],"overexpression":[423],"FLIPlong":[425],"significantly":[431],"reduce":[432],"Conclusions:":[436],"These":[437],"studies":[438],"show":[439],"complex":[440],"interactions":[441],"(TNFR1)":[452],"signals":[453],"may":[454,490],"interact":[455],"at":[456],"level":[458],"IkB,":[460],"but":[461],"exact":[463],"remains":[465],"be":[467,491],"determined.":[468],"data":[470,481],"obtained":[471],"suggest":[474,483],"additional":[476],"pathways":[477],"are":[478],"involved.":[479],"combinations":[485],"exploited":[492],"therapeutically":[493],"(showing":[498],"up-regulation":[499],"TNFa)":[500],"eliminating":[502],"primarily":[503],"clonal":[504],"protecting":[507],"hemopoiesis.":[509],"Figure":[510,511]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2020-04-24T00:00:00"}