{"id":"https://openalex.org/W59029631","doi":"https://doi.org/10.1182/blood.v122.21.1459.1459","title":"Growth Inhibitory Function Of a Novel T-LAK Cell-Originated Protein Kinase Inhibitor On FLT3-ITD Positive Acute Myeloid Leukemia (AML) Cells","display_name":"Growth Inhibitory Function Of a Novel T-LAK Cell-Originated Protein Kinase Inhibitor On FLT3-ITD Positive Acute Myeloid Leukemia (AML) Cells","publication_year":2013,"publication_date":"2013-11-15","ids":{"openalex":"https://openalex.org/W59029631","doi":"https://doi.org/10.1182/blood.v122.21.1459.1459","mag":"59029631"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v122.21.1459.1459","doi":"https://doi.org/10.1182/blood.v122.21.1459.1459","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v122.21.1459.1459","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/A5003617778","display_name":"Houda Alachkar","orcid":"https://orcid.org/0000-0001-5567-5521","observed_orcids":["https://orcid.org/0000-0001-5567-5521"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Houda Alachkar","raw_affiliation_strings":["University of Chicago , Chicago, IL, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Chicago , Chicago, IL, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Jae-Hyun Park","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jae-Hyun Park","raw_affiliation_strings":["University of Chicago , Chicago, IL, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Chicago , Chicago, IL, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008513060","display_name":"Makoto Nakakido","orcid":"https://orcid.org/0000-0003-0328-9914","observed_orcids":["https://orcid.org/0000-0003-0328-9914"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Makoto Nakakido","raw_affiliation_strings":["University of Chicago , Chicago, IL, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Chicago , Chicago, IL, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110089004","display_name":"Alex Wood","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Alex Wood","raw_affiliation_strings":["University of Chicago , Chicago, IL, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Chicago , Chicago, IL, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102946965","display_name":"Gordana Raca","orcid":"https://orcid.org/0000-0002-5259-1784","observed_orcids":["https://orcid.org/0000-0002-5259-1784"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Gordana Raca","raw_affiliation_strings":["Department of Medicine, University of Chicago, Chicago, IL, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, University of Chicago, Chicago, IL, USA,","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5057282547","display_name":"Yo Matsuo","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210091569","display_name":"OncoTherapy Science (Japan)","ror":"https://ror.org/000znbq58","country_code":"JP","type":"company","lineage":["https://openalex.org/I4210091569"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Yo Matsuo","raw_affiliation_strings":["OncoTherapy Science, Inc., Kanagawa, Japan,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"OncoTherapy Science, Inc., Kanagawa, Japan,","institution_ids":["https://openalex.org/I4210091569"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005939966","display_name":"Wendy Stock","orcid":"https://orcid.org/0000-0002-8349-9200","observed_orcids":["https://orcid.org/0000-0002-8349-9200"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Wendy Stock","raw_affiliation_strings":["Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5101940701","display_name":"Yusuke Nakamura","orcid":"https://orcid.org/0009-0009-8461-749X","observed_orcids":["https://orcid.org/0009-0009-8461-749X","https://orcid.org/0000-0003-2956-382X","https://orcid.org/0000-0002-2310-0587","https://orcid.org/0000-0003-4425-4216","https://orcid.org/0009-0004-6320-7030"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Yusuke Nakamura","raw_affiliation_strings":["University of Chicago , Chicago, IL, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Chicago , Chicago, IL, USA","institution_ids":["https://openalex.org/I40347166"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5003617778","https://openalex.org/A5008513060","https://openalex.org/A5057282547","https://openalex.org/A5101940701","https://openalex.org/A5110089004"],"corresponding_institution_ids":["https://openalex.org/I40347166","https://openalex.org/I4210091569"],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.00745405,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"122","issue":"21","first_page":"1459","last_page":"1459"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.9990000128746033,"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"}},"topics":[{"id":"https://openalex.org/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.9990000128746033,"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/T11559","display_name":"Retinoids in leukemia and cellular processes","score":0.00019999999494757503,"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/T13779","display_name":"Cancer Mechanisms and Therapy","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/2734","display_name":"Pathology and Forensic Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/topk","display_name":"TOPK","score":0.9020000100135803},{"id":"https://openalex.org/keywords/acute-myeloid-leukemia","display_name":"acute myeloid leukemia","score":0.9169999957084656},{"id":"https://openalex.org/keywords/flt3-itd-mutation","display_name":"FLT3-ITD","score":0.8899999856948853},{"id":"https://openalex.org/keywords/protein-kinase-inhibitors","display_name":"protein kinase inhibitors","score":0.7350000143051147},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.6980000138282776},{"id":"https://openalex.org/keywords/cell-viability","display_name":"cell viability","score":0.7900000214576721},{"id":"https://openalex.org/keywords/cell-differentiation","display_name":"cell differentiation","score":0.6930000185966492},{"id":"https://openalex.org/keywords/sirna-knockdown","display_name":"siRNA knockdown","score":0.7960000038146973},{"id":"https://openalex.org/keywords/mv4-11-cells","display_name":"MV4-11 cells","score":0.746999979019165},{"id":"https://openalex.org/keywords/u937-cells","display_name":"U937 cells","score":0.906000018119812},{"id":"https://openalex.org/keywords/molm-13-cells","display_name":"MOLM-13 cells","score":0.7229999899864197},{"id":"https://openalex.org/keywords/drug-sensitivity","display_name":"drug sensitivity","score":0.5239999890327454},{"id":"https://openalex.org/keywords/targeted-therapy","display_name":"targeted therapy","score":0.43299999833106995},{"id":"https://openalex.org/keywords/mapk-kinase","display_name":"MAPK kinase","score":0.35100001096725464},{"id":"https://openalex.org/keywords/gene-expression-profiling","display_name":"gene expression profiling","score":0.35100001096725464}],"concepts":[{"id":"https://openalex.org/C2778729363","wikidata":"https://www.wikidata.org/wiki/Q11688946","display_name":"Myeloid leukemia","level":2,"score":0.7235249280929565},{"id":"https://openalex.org/C53227056","wikidata":"https://www.wikidata.org/wiki/Q189152","display_name":"Viability assay","level":3,"score":0.6737826466560364},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5326829552650452},{"id":"https://openalex.org/C2778461978","wikidata":"https://www.wikidata.org/wiki/Q29496","display_name":"Leukemia","level":2,"score":0.4976995289325714},{"id":"https://openalex.org/C2780670749","wikidata":"https://www.wikidata.org/wiki/Q14908239","display_name":"Annexin A5","level":4,"score":0.45543795824050903},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.4416937232017517},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.4393320083618164},{"id":"https://openalex.org/C54009773","wikidata":"https://www.wikidata.org/wiki/Q1429031","display_name":"Transfection","level":3,"score":0.4315505027770996},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.41008636355400085},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.3864744305610657},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3795398473739624},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.3369525074958801},{"id":"https://openalex.org/C88634738","wikidata":"https://www.wikidata.org/wiki/Q24769543","display_name":"Annexin","level":3,"score":0.32673048973083496},{"id":"https://openalex.org/C553184892","wikidata":"https://www.wikidata.org/wiki/Q1141429","display_name":"Flow cytometry","level":2,"score":0.1616676151752472},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.07997047901153564},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v122.21.1459.1459","doi":"https://doi.org/10.1182/blood.v122.21.1459.1459","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v122.21.1459.1459","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":[{"score":0.9922999739646912,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"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/W2307117135","https://openalex.org/W1918089396","https://openalex.org/W2919049258","https://openalex.org/W2575628175","https://openalex.org/W1981906930","https://openalex.org/W2983483153","https://openalex.org/W3078791573","https://openalex.org/W1884906053","https://openalex.org/W2533674945","https://openalex.org/W4206144617"],"abstract_inverted_index":{"Abstract":[0],"T-LAK":[1],"cell-originated":[2],"protein":[3,9,83,500,515,572,589],"kinase":[4,10,11,195,557],"(TOPK/PBK),":[5],"a":[6,42,131,399,416,596],"serine-threonine":[7],"mitogen-activated":[8],"is":[12,27,39,196,542,577],"highly":[13,543],"expressed":[14,544],"and":[15,35,52,67,142,145,149,153,173,216,267,293,297,301,316,323,327,344,352,384,441,465,483,494,511,526,547],"correlated":[16],"with":[17,160,186,210,229,237,262,280,287,308,373,392,426,433,438,444,462,523,607],"more":[18,271],"aggressive":[19],"disease":[20,57],"in":[21,29,41,56,65,84,99,112,127,136,165,176,224,257,342,350,354,368,388,436,450,453,458,477,484,520,545],"several":[22],"types":[23],"of":[24,44,63,81,102,125,133,232,250,290,335,382,394,428,498,529,570,605],"cancer,":[25],"but":[26],"undetectable":[28],"normal":[30],"tissues":[31],"except":[32],"the":[33,61,70,78,123,211,233,246,274,291,306,309,336,365,395,429,459,463,473,478,492,495,502,509,512,530,581,585],"testis":[34],"fetal":[36],"tissues.":[37],"TOPK":[38,64,82,92,108,126,194,412,434,466,541,556],"up-regulated":[40],"variety":[43],"hematologic":[45],"malignancies":[46],"including":[47],"acute":[48],"myeloid":[49],"leukemia":[50],"(AML)":[51],"may":[53,548,594],"be":[54],"involved":[55,452],"pathogenesis.":[58],"To":[59,121,397],"investigate":[60],"role":[62,124],"AML":[66,85,104,138,207,241,374,546,565],"to":[68,183,273,277,348,410,562,579],"develop":[69],"rationale":[71],"for":[72,201,213,314,325,600],"therapeutic":[73,552],"targeting,":[74],"we":[75,129,414,505],"initially":[76],"examined":[77,491],"expression":[79,93,418,496],"level":[80],"cell":[86,105,139,147,166,171,208,225,242,251,278,321,331,454],"lines":[87,140,209,261,279],"by":[88,151,220,254,299,340,583],"western":[89],"blot":[90],"analysis.":[91],"was":[94,109,235,312,471],"detected":[95,111],"at":[96,357],"high":[97],"levels":[98,497,516],"8":[100],"out":[101],"11":[103],"lines.":[106,243],"Importantly,":[107],"not":[110],"mobilized,":[113],"peripheral":[114],"blood-derived":[115],"stem":[116],"cells":[117,184,218,286,295,318,346,406,424,440,442,481,487,521],"from":[118,371],"healthy":[119],"donors.":[120],"determine":[122,580],"AML,":[128],"utilized":[130],"loss":[132],"function":[134],"approach":[135],"two":[137],"(MV4-11":[141],"U937":[143,258,326,351],"cells)":[144],"assessed":[146,217,253,294],"viability":[148,167,219,226,296],"apoptosis":[150,177,298,339,389],"MTS":[152,221,300],"Annexin/PI":[154],"staining":[155,256],"assays,":[156],"respectively.":[157],"Cells":[158],"transfected":[159,185,432,443,486],"TOPK-siRNA":[161,485],"showed":[162,248,385],"significant":[163,174,448],"decrease":[164],"(\u223c70%,":[168],"P<0.001,":[169],"both":[170,508],"lines)":[172],"increase":[175,387],"48":[178,214,358],"hours":[179,215,359,536],"following":[180,227,360,390,501,537],"transfection":[181],"compared":[182,276,347],"control-siRNA.":[187,445],"A":[188,554],"small":[189],"molecule":[190],"compound":[191,212,234,247,292,337,430,479,531,586,593],"that":[192,507],"inhibits":[193,587],"currently":[197],"undergoing":[198],"pharmaceutical":[199],"development":[200],"cancer":[202],"treatment.":[203,361,503,538],"We":[204,283,362,446,489],"treated":[205,285,425,480,522],"nine":[206],"assay.":[222],"Decrease":[223],"treatment":[228,275,307,391],"increasing":[230,288],"doses":[231,289],"noted":[236],"variable":[238],"sensitivities":[239],"among":[240,472],"In":[244,539],"addition,":[245],"enhancement":[249],"differentiation":[252],"CD11b":[255],"cells.":[259,468],"Cell":[260],"FLT3":[263,470,499,514,571,588],"mutations":[264],"(MV4-11,":[265],"MOLM13":[266,317,345],"KOCL-48)":[268],"were":[269,517],"significantly":[270,474],"sensitive":[272,409],"unmutated":[281],"FLT3.":[282],"next":[284],"flow":[302],"cytometry":[303],"assays.":[304],"Following":[305],"compound,":[310],"IC50":[311,381],"<10nM":[313],"MV4-11":[315,343,423],"(FLT3-ITD":[319,329],"positive":[320,377],"lines),":[322],">20nM":[324],"KG1":[328,355],"negative":[330],"lines).":[332],"40":[333,527],"nM":[334,528],"induced":[338],"\u223c80%":[341],"49%":[349],"9%":[353],"cells,":[356,566],"also":[363],"validated":[364],"anti-leukemia":[366],"activity":[367,493],"primary":[369],"blasts":[370,378],"patients":[372,606],"(n=2).":[375],"FLT3-ITD":[376,404,563],"had":[379],"an":[380],"\u223c15nM":[383],"40%":[386],"20nM":[393,427],"compound.":[396],"gain":[398],"mechanistic":[400],"insight":[401],"into":[402],"why":[403],"mutant":[405],"are":[407],"preferentially":[408],"this":[411,591,601],"inhibitor,":[413],"performed":[415],"gene":[417],"profile":[419],"microarray":[420],"analysis":[421],"on":[422],"or":[431],"siRNA":[435],"comparison":[437],"untreated":[439],"observed":[447],"downregulation":[449],"genes":[451,476],"cycle":[455],"control":[456],"pathways":[457],"signatures":[460],"associated":[461],"compound-treated":[464],"siRNA-transfected":[467],"Interestingly,":[469],"downregulated":[475],"(\u223c80%)":[482],"(\u223c30%).":[488],"then":[490],"Consistently,":[504],"found":[506],"phospho-FLT3":[510],"total":[513],"completely":[518],"depleted":[519],"10,":[524],"20":[525],"as":[532,534,550],"early":[533],"16":[535],"conclusion,":[540],"act":[549],"novel":[551,555,592],"target.":[553],"inhibitor":[558],"exhibits":[559],"preferential":[560],"cytotoxicity":[561],"mutated":[564],"possibly":[567],"through":[568],"inhibition":[569],"expression.":[573],"Although":[574],"further":[575],"research":[576],"needed":[578],"mechanism":[582],"which":[584],"expression,":[590],"represent":[595],"new":[597],"targeted":[598],"therapy":[599],"adverse":[602],"risk":[603],"subset":[604],"AML.":[608],"Disclosures:":[609],"Matsuo:":[610],"OncoTherapy":[611],"Science,":[612],"Inc.:":[613],"Employment.":[614],"Nakamura:Oncotherapy":[615],"Science.":[616],"Ltd.:":[617],"share":[618],"holder":[619],"Other.":[620]},"counts_by_year":[],"updated_date":"2026-11-05T12:25:35.769452","created_date":"2016-06-24T00:00:00"}
