{"id":"https://openalex.org/W2989235017","doi":"https://doi.org/10.1182/blood-2019-127047","title":"Paics, a De Novo Purine Synthetic Enzyme, Is a Novel Target for AML Therapy","display_name":"Paics, a De Novo Purine Synthetic Enzyme, Is a Novel Target for AML Therapy","publication_year":2019,"publication_date":"2019-11-13","ids":{"openalex":"https://openalex.org/W2989235017","doi":"https://doi.org/10.1182/blood-2019-127047","mag":"2989235017"},"language":"en","primary_location":{"id":"doi:10.1182/blood-2019-127047","doi":"https://doi.org/10.1182/blood-2019-127047","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2019-127047","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":"conference-abstract","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/A5044491408","display_name":"Takuji Yamauchi","orcid":"https://orcid.org/0000-0002-6238-3145","observed_orcids":["https://orcid.org/0000-0002-6238-3145"]},"institutions":[{"id":"https://openalex.org/I135598925","display_name":"Kyushu University","ror":"https://ror.org/00p4k0j84","country_code":"JP","type":"education","lineage":["https://openalex.org/I135598925"]},{"id":"https://openalex.org/I4210097767","display_name":"Kyushu University Hospital","ror":"https://ror.org/00ex2fc97","country_code":"JP","type":"healthcare","lineage":["https://openalex.org/I135598925","https://openalex.org/I4210097767"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Takuji Yamauchi","raw_affiliation_strings":["Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan","Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan","institution_ids":["https://openalex.org/I135598925","https://openalex.org/I4210097767"]},{"raw_affiliation_string":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan","institution_ids":["https://openalex.org/I135598925"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5033736868","display_name":"Kohta Miyawaki","orcid":"https://orcid.org/0000-0003-0526-4016","observed_orcids":["https://orcid.org/0000-0003-0526-4016"]},"institutions":[{"id":"https://openalex.org/I135598925","display_name":"Kyushu University","ror":"https://ror.org/00p4k0j84","country_code":"JP","type":"education","lineage":["https://openalex.org/I135598925"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Kohta Miyawaki","raw_affiliation_strings":["Department of Medicine and Biosystemic Science, Kyushu University, Fukuoka, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine and Biosystemic Science, Kyushu University, Fukuoka, Japan","institution_ids":["https://openalex.org/I135598925"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5001450764","display_name":"Yuichiro Semba","orcid":"https://orcid.org/0000-0001-8576-3530","observed_orcids":["https://orcid.org/0000-0001-8576-3530"]},"institutions":[{"id":"https://openalex.org/I135598925","display_name":"Kyushu University","ror":"https://ror.org/00p4k0j84","country_code":"JP","type":"education","lineage":["https://openalex.org/I135598925"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Yuichiro Semba","raw_affiliation_strings":["Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan","institution_ids":["https://openalex.org/I135598925"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5020573083","display_name":"Fumihiko Nakao","orcid":"https://orcid.org/0000-0003-4216-4460","observed_orcids":["https://orcid.org/0000-0003-4216-4460"]},"institutions":[{"id":"https://openalex.org/I135598925","display_name":"Kyushu University","ror":"https://ror.org/00p4k0j84","country_code":"JP","type":"education","lineage":["https://openalex.org/I135598925"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Fumihiko Nakao","raw_affiliation_strings":["Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan","institution_ids":["https://openalex.org/I135598925"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5007481238","display_name":"Takeshi Sugio","orcid":"https://orcid.org/0000-0002-4270-1943","observed_orcids":["https://orcid.org/0000-0002-4270-1943"]},"institutions":[{"id":"https://openalex.org/I135598925","display_name":"Kyushu University","ror":"https://ror.org/00p4k0j84","country_code":"JP","type":"education","lineage":["https://openalex.org/I135598925"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Takeshi Sugio","raw_affiliation_strings":["Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan","institution_ids":["https://openalex.org/I135598925"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046240605","display_name":"Kensuke Sasaki","orcid":"https://orcid.org/0000-0003-1302-3511","observed_orcids":["https://orcid.org/0000-0003-1302-3511"]},"institutions":[{"id":"https://openalex.org/I135598925","display_name":"Kyushu University","ror":"https://ror.org/00p4k0j84","country_code":"JP","type":"education","lineage":["https://openalex.org/I135598925"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Kensuke Sasaki","raw_affiliation_strings":["Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan","institution_ids":["https://openalex.org/I135598925"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070685245","display_name":"Jumpei Nogami","orcid":"https://orcid.org/0000-0001-9050-7734","observed_orcids":["https://orcid.org/0000-0001-9050-7734"]},"institutions":[{"id":"https://openalex.org/I135598925","display_name":"Kyushu University","ror":"https://ror.org/00p4k0j84","country_code":"JP","type":"education","lineage":["https://openalex.org/I135598925"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Jumpei Nogami","raw_affiliation_strings":["Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan","institution_ids":["https://openalex.org/I135598925"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5071212287","display_name":"Matthew C. Canver","orcid":"https://orcid.org/0000-0002-8146-3992","observed_orcids":["https://orcid.org/0000-0002-8146-3992"]},"institutions":[{"id":"https://openalex.org/I1288882113","display_name":"Boston Children's Hospital","ror":"https://ror.org/00dvg7y05","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1288882113"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Matthew C. Canver","raw_affiliation_strings":["Division of Hematology/Oncology, Boston Children's Hospital/Harvard Medical School, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology/Oncology, Boston Children's Hospital/Harvard Medical School, Boston, MA","institution_ids":["https://openalex.org/I1288882113","https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5020419534","display_name":"Simon A. Osborne","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I109541847","display_name":"LifeArc","ror":"https://ror.org/01dqb0q37","country_code":"GB","type":"nonprofit","lineage":["https://openalex.org/I109541847"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Simon Osborne","raw_affiliation_strings":["LifeArc, London, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"LifeArc, London, United Kingdom","institution_ids":["https://openalex.org/I109541847"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5078228499","display_name":"Luca Pinello","orcid":"https://orcid.org/0000-0003-1109-3823","observed_orcids":["https://orcid.org/0000-0003-1109-3823"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Luca Pinello","raw_affiliation_strings":["Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210087915"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Deborah Taylor","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I109541847","display_name":"LifeArc","ror":"https://ror.org/01dqb0q37","country_code":"GB","type":"nonprofit","lineage":["https://openalex.org/I109541847"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Deborah Taylor","raw_affiliation_strings":["LifeArc, London, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"LifeArc, London, United Kingdom","institution_ids":["https://openalex.org/I109541847"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5071805086","display_name":"Daniel E. Bauer","orcid":"https://orcid.org/0000-0001-5076-7945","observed_orcids":["https://orcid.org/0000-0001-5076-7945"]},"institutions":[{"id":"https://openalex.org/I1288882113","display_name":"Boston Children's Hospital","ror":"https://ror.org/00dvg7y05","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1288882113"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Daniel E. Bauer","raw_affiliation_strings":["Division of Hematology/Oncology, Boston Children's Hospital/Harvard Medical School, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology/Oncology, Boston Children's Hospital/Harvard Medical School, Boston, MA","institution_ids":["https://openalex.org/I1288882113","https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102870989","display_name":"Koichi Akashi","orcid":"https://orcid.org/0000-0001-7763-5723","observed_orcids":["https://orcid.org/0000-0001-7763-5723"]},"institutions":[{"id":"https://openalex.org/I135598925","display_name":"Kyushu University","ror":"https://ror.org/00p4k0j84","country_code":"JP","type":"education","lineage":["https://openalex.org/I135598925"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Koichi Akashi","raw_affiliation_strings":["Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan","institution_ids":["https://openalex.org/I135598925"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5035237919","display_name":"Takahiro Maeda","orcid":"https://orcid.org/0000-0003-4530-6460","observed_orcids":["https://orcid.org/0000-0003-4530-6460"]},"institutions":[{"id":"https://openalex.org/I135598925","display_name":"Kyushu University","ror":"https://ror.org/00p4k0j84","country_code":"JP","type":"education","lineage":["https://openalex.org/I135598925"]},{"id":"https://openalex.org/I4210097767","display_name":"Kyushu University Hospital","ror":"https://ror.org/00ex2fc97","country_code":"JP","type":"healthcare","lineage":["https://openalex.org/I135598925","https://openalex.org/I4210097767"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Takahiro Maeda","raw_affiliation_strings":["Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan","institution_ids":["https://openalex.org/I135598925","https://openalex.org/I4210097767"]}]}],"institutions":[],"countries_distinct_count":3,"institutions_distinct_count":6,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":2,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"134","issue":"Supplement_1","first_page":"1390","last_page":"1390"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.9146000146865845,"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":0.9146000146865845,"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/T12827","display_name":"Biochemical and Molecular Research","score":0.06780000030994415,"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/T11559","display_name":"Retinoids in leukemia and cellular processes","score":0.001500000013038516,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/acute-myeloid-leukemia","display_name":"acute myeloid leukemia","score":0.8870000243186951},{"id":"https://openalex.org/keywords/paics","display_name":"PAICS","score":0.953000009059906},{"id":"https://openalex.org/keywords/de-novo-purine-synthesis","display_name":"de novo purine synthesis","score":0.9559999704360962},{"id":"https://openalex.org/keywords/patient-derived-xenografts","display_name":"patient-derived xenografts","score":0.7879999876022339},{"id":"https://openalex.org/keywords/drug-target-identification","display_name":"drug target identification","score":0.5239999890327454},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.5120000243186951},{"id":"https://openalex.org/keywords/cell-cycle","display_name":"cell cycle","score":0.4830000102519989},{"id":"https://openalex.org/keywords/mll-af9","display_name":"MLL-AF9","score":0.4399999976158142}],"concepts":[{"id":"https://openalex.org/C98108389","wikidata":"https://www.wikidata.org/wiki/Q412563","display_name":"CRISPR","level":3,"score":0.81402987241745},{"id":"https://openalex.org/C144501496","wikidata":"https://www.wikidata.org/wiki/Q5533489","display_name":"Genome editing","level":4,"score":0.6182041168212891},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5715618133544922},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.4687611758708954},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.46635451912879944},{"id":"https://openalex.org/C132455925","wikidata":"https://www.wikidata.org/wiki/Q16965677","display_name":"Cas9","level":4,"score":0.45532938838005066},{"id":"https://openalex.org/C141231307","wikidata":"https://www.wikidata.org/wiki/Q7020","display_name":"Genome","level":3,"score":0.4402678608894348},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4317364990711212},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.42164111137390137},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.40355491638183594},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.36195504665374756}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood-2019-127047","doi":"https://doi.org/10.1182/blood-2019-127047","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2019-127047","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":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9476000070571899}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W3191467773","https://openalex.org/W3183235432","https://openalex.org/W2970797648","https://openalex.org/W2979692056","https://openalex.org/W2971543368","https://openalex.org/W4394617735","https://openalex.org/W2788791702","https://openalex.org/W3200090243","https://openalex.org/W2985428641","https://openalex.org/W3211436691"],"abstract_inverted_index":{"Progress":[0],"has":[1],"been":[2],"made":[3],"in":[4,12,74,174,235,250,256,270,302,381,405,429,442,458,489,512,536],"deciphering":[5],"molecular":[6],"mechanisms":[7],"underlying":[8],"AML":[9,18,21,52,63,110,160,184,195,207,259,271,277,303,315,324,341,492,499,535,548,570],"pathogenesis":[10],"due":[11,97],"part":[13],"to":[14,91,98,287,364,417,433],"near-complete":[15],"understanding":[16],"of":[17,32,43,153,206,216,225,238,267,299,310,336,384,445,454,476,487,518,529,532,556],"genomes.":[19],"However,":[20],"is":[22,179,564],"yet":[23],"a":[24,28,71,99,146,180,188,230,283,296,391,565],"devastating":[25],"disease":[26],"with":[27,198],"long-term":[29],"survival":[30,205,273],"rate":[31],"less":[33],"than":[34,525],"30%,":[35],"underscoring":[36],"an":[37,171,544],"urgent":[38],"need":[39],"for":[40,51,183,242,547,569],"the":[41,125,130,143,213,236,264,360,372,382,426,430,443,459,477,508,557],"development":[42],"additional":[44,219],"therapeutic":[45,530,567],"modalities.":[46],"To":[47],"identify":[48],"novel":[49],"targets":[50],"therapy,":[53],"we":[54,81,128,211,482,540],"performed":[55,377],"genome-wide":[56,149,231,378],"CRISPR-Cas9":[57,150,222,353,379],"dropout":[58,233],"screens":[59,380,389],"employing":[60,218],"two":[61,77,497],"mouse":[62],"cell":[64,78,111,155,161,185,196,253,272,316,327,342,346,549],"lines":[65,112,156,197],"(CALM/AF10":[66],"and":[67,113,202,229,255,330,332,349,437,515],"MLL/AF9),":[68],"followed":[69,386],"by":[70,387,507],"second":[72,388],"screen":[73,151,234],"vivo.":[75,537],"These":[76],"lines,":[79],"which":[80,169,455],"established,":[82],"harbor":[83],"wild-type":[84],"(WT)":[85],"Trp53with":[86],"normal":[87],"karyotype,":[88],"enabling":[89],"us":[90],"interpret":[92],"screening":[93,131],"results":[94,132],"more":[95],"easily":[96],"\"clean\"":[100],"genetic":[101,200],"background.":[102],"We":[103,163,261,305,322,375,551],"then":[104,262],"validated":[105],"our":[106],"findings":[107],"using":[108,320,390,491],"human":[109,159,498],"patient-derived":[114],"xenograft":[115],"(PDX)":[116],"models":[117,494],"(Yamauchi":[118],"et":[119,138],"al.":[120,139],"Cancer":[121],"Cell":[122],"2018).":[123],"In":[124,447,538],"current":[126],"study,":[127],"assessed":[129,263,323],"furtherusing":[133],"MAGeCK":[134],"MLE":[135],"program":[136],"(Li":[137],"Genome":[140],"Biology":[141],"2015)and":[142],"DepMap":[144],"(https://depmap.org/),":[145],"publicly":[147],"available":[148],"datasets":[152],"cancer":[154],"including":[157],"15":[158],"lines.":[162,500],"show":[164],"that":[165,334,357,467,553],"PAICS":[166,190,268,280,300,311,337,365,418,542],"(Phosphoribosylaminoimidazole":[167],"carboxylase),":[168],"encodes":[170],"enzyme":[172],"involved":[173,404],"de":[175],"novo":[176],"purine":[177,460,478,559],"biosynthesis,":[178],"molecule":[181],"essential":[182,545],"survival.":[186,550],"MRT252040,":[187],"newly-developed":[189],"inhibitor":[191],"(PAICSi),":[192],"efficiently":[193],"killed":[194],"different":[199],"backgrounds":[201],"significantly":[203,248,369,464,523],"prolonged":[204],"PDX":[208,493],"models.":[209],"Furthermore,":[210],"investigated":[212],"mechanism":[214],"action":[215],"PAICSi":[217,406,434,488,501,563],"functional":[220,265],"screens:":[221],"mutagenesis":[223,354],"scan":[224,355],"all":[226],"Paicscoding":[227],"exons":[228],"CRISPR/Cas9":[232],"presence":[237,383,444],"PAICSi.":[239,321,446],"Read":[240],"counts":[241],"each":[243],"Paics-targeted":[244],"single-guide":[245],"RNA":[246],"(sgRNA)":[247],"decreased":[249,370],"vitro":[251],"(AML":[252],"lines)":[254],"vivo":[257,490],"(mouse":[258],"model).":[260],"significance":[266],"inhibition":[269,309,335],"via":[274,344,562],"shRNA-mediated":[275],"PAICSknockdown.":[276],"cells":[278,289],"expressing":[279,292],"shRNA":[281],"exhibited":[282,502],"proliferative":[284],"disadvantage":[285],"compared":[286],"non-transduced":[288],"or":[290],"those":[291,411],"scrambled":[293],"shRNA,":[294],"indicating":[295,466],"toxic":[297],"effect":[298],"depletion":[301],"cells.":[304],"next":[306,376],"asked":[307],"whether":[308],"enzymatic":[312,338,366],"activity":[313,339,367],"affects":[314],"proliferation":[317,343],"and/or":[318],"apoptosis":[319,331],"growth":[325],"rate,":[326],"cycle":[328,347],"status":[329],"found":[333],"delays":[340],"inducing":[345],"arrest":[348],"apoptosis.":[350],"As":[351],"expected,":[352],"showed":[356],"sgRNAs":[358,397,438,449],"targeting":[359,439,450,555],"exonic":[361],"regions":[362],"relevant":[363,432],"were":[368,463],"after":[371],"16-day":[373],"incubation.":[374],"PAICSi,":[385],"small-scale":[392],"sgRNA":[393],"library":[394],"containing":[395],"8-10":[396],"per":[398],"candidate":[399],"gene.We":[400],"identified":[401,541],"genes":[402,431],"potentially":[403],"resistance":[407,435],"as":[408,410,505,543],"well":[409],"whose":[412],"loss":[413],"are":[414,456],"synthetic":[415],"lethal":[416],"inhibition.":[419],"X-box-binding":[420],"protein":[421],"1":[422],"(Xbp1)":[423],"was":[424],"among":[425],"top":[427],"hits":[428],"genes,":[436],"Xbp1significantly":[440],"enriched":[441],"contrast,":[448],"Slc43a3or":[451],"Hprt,":[452],"both":[453],"implicated":[457],"salvage":[461,479],"pathway,":[462],"dropped-out,":[465],"PAICSi-mediated":[468],"anti-leukemia":[469,485],"effects":[470,486],"can":[471],"be":[472],"enhanced":[473],"upon":[474],"concurrentinhibition":[475],"pathway.":[480],"Finally,":[481],"explored":[483],"potential":[484,566],"established":[495],"from":[496],"anti-leukemic":[503],"activity,":[504],"evidenced":[506],"lower":[509],"leukemia":[510],"burden":[511],"peripheral":[513],"blood":[514],"bone":[516],"marrow":[517],"PAICSi-treated":[519],"mice.":[520],"They":[521],"survived":[522],"longer":[524],"vehicle-treated":[526],"mice,":[527],"indicative":[528],"efficacy":[531],"PAICSimonotherapy":[533],"against":[534],"summary,":[539],"gene":[546],"propose":[552],"pharmacological":[554],"de-novo":[558],"synthesis":[560],"pathway":[561],"strategy":[568],"therapy.":[571],"Disclosures":[572],"Akashi:":[573],"Celgene,":[574],"Kyowa":[575,588],"Kirin,":[576],"Astellas,":[577],"Shionogi,":[578],"Asahi":[579],"Kasei,":[580],"Chugai,":[581],"Bristol-Myers":[582],"Squibb:":[583],"Research":[584],"Funding;":[585],"Sumitomo":[586],"Dainippon,":[587],"Kirin:":[589],"Consultancy.":[590]},"counts_by_year":[{"year":2023,"cited_by_count":2}],"updated_date":"2026-09-29T14:09:16.559479","created_date":"2019-11-22T00:00:00"}
