{"id":"https://openalex.org/W4310167602","doi":"https://doi.org/10.1182/blood-2022-170721","title":"Fatty Acid Desaturation Is a Metabolic Vulnerability of Acute Myeloid Leukemia Cells","display_name":"Fatty Acid Desaturation Is a Metabolic Vulnerability of Acute Myeloid Leukemia Cells","publication_year":2022,"publication_date":"2022-11-15","ids":{"openalex":"https://openalex.org/W4310167602","doi":"https://doi.org/10.1182/blood-2022-170721"},"language":"en","primary_location":{"id":"doi:10.1182/blood-2022-170721","doi":"https://doi.org/10.1182/blood-2022-170721","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2022-170721","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/A5044433777","display_name":"Joice S. Kanefsky","orcid":"https://orcid.org/0000-0002-7913-3951","observed_orcids":["https://orcid.org/0000-0002-7913-3951"]},"institutions":[{"id":"https://openalex.org/I1289437631","display_name":"Fox Chase Cancer Center","ror":"https://ror.org/0567t7073","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1289437631","https://openalex.org/I4210122924"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Joice Kanefsky","raw_affiliation_strings":["1Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA","institution_ids":["https://openalex.org/I1289437631"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000715606","display_name":"Yorrick R. J. Jaspers","orcid":"https://orcid.org/0000-0002-9153-5734","observed_orcids":["https://orcid.org/0000-0002-9153-5734"]},"institutions":[{"id":"https://openalex.org/I4210151833","display_name":"Amsterdam University Medical Centers","ror":"https://ror.org/05grdyy37","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I4210151833"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Yorrick Jaspers","raw_affiliation_strings":["2Amsterdam University Medical Centers, Amsterdam, Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Amsterdam University Medical Centers, Amsterdam, Netherlands","institution_ids":["https://openalex.org/I4210151833"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009500330","display_name":"Esteban Mart\u0131\u0301nez","orcid":"https://orcid.org/0000-0002-4798-3548","observed_orcids":["https://orcid.org/0000-0002-4798-3548"]},"institutions":[{"id":"https://openalex.org/I1289437631","display_name":"Fox Chase Cancer Center","ror":"https://ror.org/0567t7073","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1289437631","https://openalex.org/I4210122924"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Esteban Martinez","raw_affiliation_strings":["1Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA","institution_ids":["https://openalex.org/I1289437631"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034859994","display_name":"Jacklyn M. Huhn","orcid":"https://orcid.org/0000-0001-7503-3040","observed_orcids":["https://orcid.org/0000-0001-7503-3040"]},"institutions":[{"id":"https://openalex.org/I1289437631","display_name":"Fox Chase Cancer Center","ror":"https://ror.org/0567t7073","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1289437631","https://openalex.org/I4210122924"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jacklyn Huhn","raw_affiliation_strings":["1Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA","institution_ids":["https://openalex.org/I1289437631"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5052474436","display_name":"Daniela Di Marcoantonio","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1289437631","display_name":"Fox Chase Cancer Center","ror":"https://ror.org/0567t7073","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1289437631","https://openalex.org/I4210122924"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Daniela Di Marcoantonio","raw_affiliation_strings":["3Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia,","institution_ids":["https://openalex.org/I1289437631"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009460971","display_name":"Stephan Kemp","orcid":"https://orcid.org/0000-0003-2023-064X","observed_orcids":["https://orcid.org/0000-0003-2023-064X"]},"institutions":[{"id":"https://openalex.org/I4210151833","display_name":"Amsterdam University Medical Centers","ror":"https://ror.org/05grdyy37","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I4210151833"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Stephan Kemp","raw_affiliation_strings":["2Amsterdam University Medical Centers, Amsterdam, Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Amsterdam University Medical Centers, Amsterdam, Netherlands","institution_ids":["https://openalex.org/I4210151833"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002152110","display_name":"David L. Wiest","orcid":"https://orcid.org/0000-0002-0792-3188","observed_orcids":["https://orcid.org/0000-0002-0792-3188"]},"institutions":[{"id":"https://openalex.org/I1289437631","display_name":"Fox Chase Cancer Center","ror":"https://ror.org/0567t7073","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1289437631","https://openalex.org/I4210122924"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David Wiest","raw_affiliation_strings":["1Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA","institution_ids":["https://openalex.org/I1289437631"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5057876965","display_name":"Stephen Matthew Sykes","orcid":"https://orcid.org/0000-0002-7330-0106","observed_orcids":["https://orcid.org/0000-0002-7330-0106"]},"institutions":[{"id":"https://openalex.org/I204465549","display_name":"Washington University in St. Louis","ror":"https://ror.org/01yc7t268","country_code":"US","type":"education","lineage":["https://openalex.org/I204465549"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Stephen M. Sykes","raw_affiliation_strings":["4Department of Pediatrics, Washington University, Saint Louis, MO"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"4Department of Pediatrics, Washington University, Saint Louis, MO","institution_ids":["https://openalex.org/I204465549"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":2500,"currency":"USD","value_usd":2500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.13724495,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"140","issue":"Supplement 1","first_page":"5885","last_page":"5886"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12465","display_name":"Cancer, Lipids, and Metabolism","score":0.9932000041007996,"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"}},"topics":[{"id":"https://openalex.org/T12465","display_name":"Cancer, Lipids, and Metabolism","score":0.9932000041007996,"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"}},{"id":"https://openalex.org/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.004800000227987766,"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/T11844","display_name":"Lipid metabolism and biosynthesis","score":0.00139999995008111,"subfield":{"id":"https://openalex.org/subfields/1303","display_name":"Biochemistry"},"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":0.9990000128746033},{"id":"https://openalex.org/keywords/fads1","display_name":"FADS1","score":0.9580000042915344},{"id":"https://openalex.org/keywords/very-long-chain-fatty-acids","display_name":"very long chain fatty acids","score":0.875},{"id":"https://openalex.org/keywords/lipid-metabolism","display_name":"lipid metabolism","score":0.7160000205039978},{"id":"https://openalex.org/keywords/cd36","display_name":"CD36","score":0.6309999823570251},{"id":"https://openalex.org/keywords/fatty-acid-import","display_name":"fatty acid import","score":0.8690000176429749},{"id":"https://openalex.org/keywords/lipid-remodeling","display_name":"lipid remodeling","score":0.5690000057220459},{"id":"https://openalex.org/keywords/leukemia-cell-differentiation","display_name":"leukemia cell differentiation","score":0.5400000214576721},{"id":"https://openalex.org/keywords/chemoresistance","display_name":"chemoresistance","score":0.7160000205039978},{"id":"https://openalex.org/keywords/prognostic-factors","display_name":"prognostic factors","score":0.8040000200271606},{"id":"https://openalex.org/keywords/metabolic-vulnerability","display_name":"metabolic vulnerability","score":0.578000009059906},{"id":"https://openalex.org/keywords/lipidomics","display_name":"lipidomics","score":0.4009999930858612},{"id":"https://openalex.org/keywords/hematopoietic-stem-and-progenitor-cells","display_name":"hematopoietic stem and progenitor cells","score":0.7540000081062317},{"id":"https://openalex.org/keywords/fatty-acid-elongation","display_name":"fatty acid elongation","score":0.453000009059906}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5818187594413757},{"id":"https://openalex.org/C2778461978","wikidata":"https://www.wikidata.org/wiki/Q29496","display_name":"Leukemia","level":2,"score":0.5262919068336487},{"id":"https://openalex.org/C28328180","wikidata":"https://www.wikidata.org/wiki/Q48196","display_name":"Stem cell","level":2,"score":0.496676504611969},{"id":"https://openalex.org/C201750760","wikidata":"https://www.wikidata.org/wiki/Q1896218","display_name":"Progenitor cell","level":3,"score":0.4575035870075226},{"id":"https://openalex.org/C109159458","wikidata":"https://www.wikidata.org/wiki/Q919283","display_name":"Haematopoiesis","level":3,"score":0.4464673697948456},{"id":"https://openalex.org/C2778729363","wikidata":"https://www.wikidata.org/wiki/Q11688946","display_name":"Myeloid leukemia","level":2,"score":0.4331352710723877},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.4322412610054016},{"id":"https://openalex.org/C173396325","wikidata":"https://www.wikidata.org/wiki/Q1501275","display_name":"Gene knockdown","level":3,"score":0.43114978075027466},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.36599069833755493},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.31758952140808105},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.2555168867111206},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.08196660876274109}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood-2022-170721","doi":"https://doi.org/10.1182/blood-2022-170721","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2022-170721","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":0.9763000011444092}],"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/W6999949570","https://openalex.org/W4393281188","https://openalex.org/W3136017577","https://openalex.org/W4401872179","https://openalex.org/W4360856474","https://openalex.org/W4310096242","https://openalex.org/W4389248000","https://openalex.org/W4386024358","https://openalex.org/W3006635774","https://openalex.org/W2900459849"],"abstract_inverted_index":{"Acute":[0],"Myeloid":[1],"Leukemia":[2],"(AML)":[3],"cells":[4,10,167,191,220,313,355,447],"-":[5,11,93,104,229],"like":[6],"many":[7],"other":[8],"cancer":[9],"exploit":[12],"lipid":[13,31,249,275,392,396],"metabolic":[14],"pathways":[15,410,430,458],"to":[16,39,70,209,324,327,390,407,432,460],"support":[17],"their":[18],"high":[19],"demands":[20],"for":[21,79,332,415],"energy":[22],"and":[23,33,112,121,141,163,177,213,240,242,255,277,291,386,439,442,467,484,503,508],"biomass,":[24],"while":[25,158,381],"maintaining":[26],"an":[27,125,325,404,519],"immature":[28],"phenotype.":[29],"Though":[30],"synthesis":[32,276],"catabolism":[34,278],"may":[35,76,412],"be":[36,77,413,461],"equally":[37],"important":[38],"sustain":[40],"AML":[41,80,111,154,190,312,488],"cell":[42,137,155],"survival,":[43],"much":[44],"of":[45,56,87,97,150,171,186,201,261,270,294,337,344,366,373,379,384,419,456,506,513,526],"the":[46,49,54,85,259,268,289,342,363,371,377,382,416,495,500,511],"focus":[47],"in":[48,110,115,139,145,274,306,353,359,487,522],"field":[50],"has":[51],"been":[52],"on":[53,317],"oxidation":[55],"fatty":[57,100,226,516],"acids":[58,227,517],"(FAs).":[59],"To":[60,257],"help":[61],"close":[62],"this":[63,523],"gap,":[64],"we":[65,129,205,266,402],"queried":[66],"publicly":[67],"available":[68],"data":[69,474,493],"identify":[71,408],"FA":[72,235,301,318,338,360],"biosynthetic":[73],"enzymes":[74,346],"that":[75,84,132,184,197,215,283,299,311,411,425,479,497,509],"essential":[78],"cells.":[81,165,308,489],"We":[82,309],"found":[83,214,246,280],"expression":[86,170,269,293],"Fatty":[88],"Acid":[89],"Desaturase":[90],"1":[91],"(FADS1)":[92],"a":[94,195,199,296],"key":[95],"regulator":[96],"highly":[98,514],"unsaturated":[99,515],"acid":[101],"(HUFA)":[102],"biosynthesis":[103,188,512],"significantly":[105],"correlates":[106],"with":[107,118],"poor":[108],"outcomes":[109],"is":[113,198,245,303],"enriched":[114],"subtypes":[116],"associated":[117],"chemotherapy":[119],"resistance":[120],"intermediate-to-poor":[122],"prognoses.":[123],"Through":[124],"shRNA-mediated":[126],"loss-of-function":[127],"approach,":[128],"have":[130],"demonstrated":[131],"FADS1":[133,151,216,264,321,420,426,498],"downregulation":[134],"slows":[135],"leukemia":[136],"proliferation":[138],"vitro":[140],"impedes":[142],"disease":[143],"propagation":[144],"vivo.":[146],"Interestingly,":[147,445],"pharmacological":[148],"inhibition":[149,486],"selectively":[152],"impairs":[153],"colony":[156],"formation":[157],"sparing":[159],"normal":[160],"hematopoietic":[161],"stem":[162],"progenitor":[164],"FADS1-deficient":[166,307,354,446],"display":[168],"increased":[169,304,464],"mature":[172],"myeloid":[173],"markers,":[174],"distinct":[175],"morphology,":[176],"superior":[178],"phagocytosis":[179],"capabilities.":[180],"These":[181,234],"results":[182],"suggest":[183],"disruption":[185],"HUFA":[187],"pushes":[189],"towards":[192],"differentiation,":[193],"overcoming":[194],"block":[196],"hallmark":[200],"malignant":[202],"hematopoiesis.":[203],"Next,":[204],"employed":[206],"mass":[207],"spectrometry":[208],"examine":[210],"complex":[211],"lipids":[212,222],"knockdown":[217],"(FADS1":[218],"KD)":[219],"accumulate":[221],"containing":[223],"very":[224],"long-chain":[225],"(VLCFAs":[228],"i.e.,":[230],"\u2265":[231],"22":[232],"carbons).":[233],"species":[236],"are":[237,471],"mostly":[238],"saturated":[239],"monounsaturated":[241],"such":[243,251,436],"accumulation":[244],"across":[247],"several":[248,271],"classes":[250],"as":[252,437],"diglycerides,":[253],"triglycerides,":[254],"phospholipids.":[256],"determine":[258],"source":[260],"VLCFAs":[262],"upon":[263],"KD,":[265],"measured":[267],"genes":[272],"involved":[273],"but":[279],"no":[281],"change":[282],"could":[284],"explain":[285],"our":[286,492],"observations.":[287],"Strikingly,":[288],"mRNA":[290],"protein":[292],"CD36,":[295],"scavenger":[297],"receptor":[298,466],"mediates":[300],"import,":[302],"4-fold":[305],"speculate":[310],"become":[314],"heavily":[315],"reliant":[316],"import":[319],"after":[320],"KD":[322,427],"due":[323],"inability":[326],"assemble":[328],"building":[329],"blocks":[330],"used":[331],"proliferation.":[333],"The":[334],"greater":[335],"influx":[336],"then":[339],"directly":[340],"boosts":[341],"activity":[343],"elongase":[345],"by":[347,463],"increasing":[348],"substrate":[349],"availability.":[350],"Lipid":[351],"remodeling":[352],"goes":[356],"beyond":[357],"changes":[358],"tails":[361],"affecting":[362],"overall":[364],"levels":[365,372],"membrane":[367,395,434,443],"structural":[368],"lipids.":[369],"Namely,":[370],"sphingomyelin":[374],"decrease":[375],"at":[376],"expense":[378],"ceramides,":[380],"proportions":[383],"phosphatidylcholine":[385],"phosphatidylinositol":[387],"increase":[388],"relative":[389],"total":[391],"pools.":[393],"Because":[394],"composition":[397],"can":[398],"influence":[399],"cellular":[400],"function,":[401],"performed":[403],"RNA-Seq":[405],"analysis":[406,423],"molecular":[409,504],"responsible":[414],"anti-leukemia":[417],"effects":[418],"downmodulation.":[421],"This":[422,454],"revealed":[424],"dramatically":[428],"upregulates":[429],"related":[431],"plasma":[433],"function":[435],"GTPase":[438],"integrin":[440],"binding,":[441],"microdomain.":[444],"activate":[448],"type":[449,525],"I":[450],"interferon":[451],"signaling":[452],"cascades.":[453],"upregulation":[455],"inflammatory":[457],"seems":[459],"caused":[462],"toll-like":[465],"STING":[468],"signaling,":[469],"which":[470],"non-redundant.":[472],"Our":[473],"corroborate":[475],"previous":[476],"findings":[477],"showing":[478],"TLR":[480],"stimulation":[481],"promotes":[482],"differentiation":[483,501],"growth":[485],"Taken":[490],"together,":[491],"supports":[494],"hypothesis":[496],"reinforces":[499],"blockade":[502],"pathogenesis":[505],"AML,":[507],"targeting":[510],"represents":[518],"exploitable":[520],"vulnerability":[521],"aggressive":[524],"blood":[527],"cancer.":[528]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2022-11-30T00:00:00"}
