{"id":"https://openalex.org/W4362484273","doi":"https://doi.org/10.1158/1541-7786.c.6545609.v1","title":"Data from Glutamine Metabolism Mediates Sensitivity to Respiratory Complex II Inhibition in Acute Myeloid Leukemia","display_name":"Data from Glutamine Metabolism Mediates Sensitivity to Respiratory Complex II Inhibition in Acute Myeloid Leukemia","publication_year":2023,"publication_date":"2023-04-03","ids":{"openalex":"https://openalex.org/W4362484273","doi":"https://doi.org/10.1158/1541-7786.c.6545609.v1"},"language":"en","primary_location":{"id":"doi:10.1158/1541-7786.c.6545609.v1","doi":"https://doi.org/10.1158/1541-7786.c.6545609.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1541-7786.c.6545609.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"volume":null,"type":"other","is_traditional":false,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1158/1541-7786.c.6545609.v1","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5028506682","display_name":"Alessia Roma","orcid":"https://orcid.org/0000-0002-5592-4724","observed_orcids":["https://orcid.org/0000-0002-5592-4724"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Alessia Roma","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-5592-4724","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014876908","display_name":"Matthew Tcheng","orcid":"https://orcid.org/0000-0001-5440-6434","observed_orcids":["https://orcid.org/0000-0001-5440-6434"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Matthew Tcheng","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0001-5440-6434","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074880093","display_name":"Nawaz Ahmed","orcid":"https://orcid.org/0000-0002-3459-0358","observed_orcids":["https://orcid.org/0000-0002-3459-0358"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Nawaz Ahmed","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-3459-0358","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101409783","display_name":"Sarah Walker","orcid":"https://orcid.org/0000-0002-9621-1763","observed_orcids":["https://orcid.org/0000-0002-9621-1763"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sarah Walker","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-9621-1763","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022634142","display_name":"Preethi Jayanth","orcid":"https://orcid.org/0000-0001-9209-7900","observed_orcids":["https://orcid.org/0000-0001-9209-7900"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Preethi Jayanth","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0001-9209-7900","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5026397928","display_name":"Mark David Minden","orcid":"https://orcid.org/0000-0002-9089-8816","observed_orcids":["https://orcid.org/0000-0002-9089-8816"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mark D. Minden","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-9089-8816","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5076562420","display_name":"Kristin J. Hope","orcid":"https://orcid.org/0000-0003-1449-4948","observed_orcids":["https://orcid.org/0000-0003-1449-4948"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Kristin Hope","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0003-1449-4948","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5017722741","display_name":"Praveen P. N. Rao","orcid":"https://orcid.org/0000-0001-5703-8251","observed_orcids":["https://orcid.org/0000-0001-5703-8251"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Praveen P. Nekkar Rao","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0001-5703-8251","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5027599762","display_name":"Jessica Luc","orcid":"https://orcid.org/0000-0003-1993-3284","observed_orcids":["https://orcid.org/0000-0003-1993-3284"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jessica Luc","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0003-1993-3284","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5032187526","display_name":"Andrew C. Doxey","orcid":"https://orcid.org/0000-0003-2015-099X","observed_orcids":["https://orcid.org/0000-0003-2015-099X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Andrew C. Doxey","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0003-2015-099X","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5015893927","display_name":"Julie A. Reisz","orcid":"https://orcid.org/0000-0002-7296-4963","observed_orcids":["https://orcid.org/0000-0002-7296-4963"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Julie A. Reisz","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-7296-4963","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5043793391","display_name":"Rachel Culp\u2010Hill","orcid":"https://orcid.org/0000-0003-3000-083X","observed_orcids":["https://orcid.org/0000-0003-3000-083X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Rachel Culp-Hill","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0003-3000-083X","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045175167","display_name":"Angelo D\u2019Alessandro","orcid":"https://orcid.org/0000-0002-2258-6490","observed_orcids":["https://orcid.org/0000-0002-2258-6490"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Angelo D'Alessandro","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-2258-6490","affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5086081617","display_name":"Paul A. Spagnuolo","orcid":"https://orcid.org/0000-0002-2431-4368","observed_orcids":["https://orcid.org/0000-0002-2431-4368"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Paul A. Spagnuolo","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-2431-4368","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.8701000213623047,"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/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.8701000213623047,"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":0.10400000214576721,"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/T10301","display_name":"Mitochondrial Function and Pathology","score":0.002099999925121665,"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":0.9990000128746033},{"id":"https://openalex.org/keywords/glutamine-metabolism","display_name":"glutamine metabolism","score":0.9539999961853027},{"id":"https://openalex.org/keywords/anaplerosis","display_name":"anaplerosis","score":0.8659999966621399},{"id":"https://openalex.org/keywords/tricarboxylic-acid-cycle","display_name":"TCA cycle","score":0.9210000038146973},{"id":"https://openalex.org/keywords/mitochondrial-electron-transport-chain","display_name":"mitochondrial electron transport chain","score":0.8519999980926514},{"id":"https://openalex.org/keywords/oxidative-phosphorylation","display_name":"oxidative phosphorylation","score":0.9399999976158142},{"id":"https://openalex.org/keywords/metabolic-reprogramming","display_name":"metabolic reprogramming","score":0.7250000238418579},{"id":"https://openalex.org/keywords/ubiquinone-binding-site","display_name":"ubiquinone binding site","score":0.7239999771118164},{"id":"https://openalex.org/keywords/small-molecule-inhibitors","display_name":"small molecule inhibitors","score":0.6570000052452087},{"id":"https://openalex.org/keywords/selective-cell-death","display_name":"selective cell death","score":0.6010000109672546},{"id":"https://openalex.org/keywords/metabolic-plasticity","display_name":"metabolic plasticity","score":0.5220000147819519}],"concepts":[{"id":"https://openalex.org/C2779349466","wikidata":"https://www.wikidata.org/wiki/Q181619","display_name":"Glutamine","level":3,"score":0.6411128044128418},{"id":"https://openalex.org/C2778729363","wikidata":"https://www.wikidata.org/wiki/Q11688946","display_name":"Myeloid leukemia","level":2,"score":0.5437082648277283},{"id":"https://openalex.org/C165135838","wikidata":"https://www.wikidata.org/wiki/Q133895","display_name":"Citric acid cycle","level":3,"score":0.5233194828033447},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5024933815002441},{"id":"https://openalex.org/C3020377403","wikidata":"https://www.wikidata.org/wiki/Q211016","display_name":"Respiratory chain","level":3,"score":0.4776916801929474},{"id":"https://openalex.org/C109159458","wikidata":"https://www.wikidata.org/wiki/Q919283","display_name":"Haematopoiesis","level":3,"score":0.43221738934516907},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.379014253616333},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3640526533126831},{"id":"https://openalex.org/C62231903","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Metabolism","level":2,"score":0.35841357707977295},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.33688029646873474},{"id":"https://openalex.org/C28859421","wikidata":"https://www.wikidata.org/wiki/Q39572","display_name":"Mitochondrion","level":2,"score":0.3324206471443176},{"id":"https://openalex.org/C515207424","wikidata":"https://www.wikidata.org/wiki/Q8066","display_name":"Amino acid","level":2,"score":0.22426742315292358},{"id":"https://openalex.org/C28328180","wikidata":"https://www.wikidata.org/wiki/Q48196","display_name":"Stem cell","level":2,"score":0.1920035183429718}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1541-7786.c.6545609.v1","doi":"https://doi.org/10.1158/1541-7786.c.6545609.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1541-7786.c.6545609.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1158/1541-7786.c.6545609.v1","doi":"https://doi.org/10.1158/1541-7786.c.6545609.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1541-7786.c.6545609.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.98580002784729}],"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/W4292641494","https://openalex.org/W6983837712","https://openalex.org/W3214159644","https://openalex.org/W7152582702","https://openalex.org/W4224230376","https://openalex.org/W1765767222","https://openalex.org/W4361946508","https://openalex.org/W2981306923","https://openalex.org/W4385330069","https://openalex.org/W7108067768"],"abstract_inverted_index":{"Abstract":[0],"Acute":[1],"myeloid":[2],"leukemia":[3],"(AML)":[4],"is":[5],"a":[6,82,84,220],"hematologic":[7],"malignancy":[8],"metabolically":[9],"dependent":[10],"on":[11],"oxidative":[12],"phosphorylation":[13],"and":[14,71,78,98,138,176,213],"mitochondrial":[15],"electron":[16],"transport":[17],"chain":[18],"(ETC)":[19],"activity.":[20],"AML":[21,45,73,112,157,210],"cells":[22,46,113,158,179],"are":[23,50],"distinct":[24],"from":[25],"their":[26],"normal":[27,116,178],"hematopoietic":[28,117],"counterparts":[29],"by":[30],"this":[31],"metabolic":[32,42,161,188,221],"reprogramming,":[33],"which":[34],"presents":[35],"targets":[36],"for":[37],"new":[38],"selective":[39,109,193,209],"therapies.":[40],"Here,":[41],"changes":[43],"in":[44,76,79,169,207],"after":[47],"ETC":[48,56],"impairment":[49],"investigated.":[51],"Genetic":[52],"knockdown":[53],"of":[54,96,106,111,130,151,172,195,203],"the":[55,92,133,146,160,187,201],"complex":[57],"II":[58],"(CII)":[59],"chaperone":[60],"protein":[61],"SDHAF1":[62],"(succinate":[63],"dehydrogenase":[64],"assembly":[65],"factor":[66],"1)":[67],"suppressed":[68],"CII":[69,97,107,131,152,205],"activity":[70,101],"delayed":[72],"cell":[74,211],"growth":[75],"vitro":[77],"vivo.":[80],"As":[81],"result,":[83],"novel":[85],"small":[86],"molecule":[87],"that":[88,125,190,223],"directly":[89],"binds":[90],"to":[91,140,144,163],"ubiquinone":[93],"binding":[94],"site":[95],"inhibits":[99],"its":[100],"was":[102],"identified.":[103],"Pharmacologic":[104],"inhibition":[105,129,150,194,206],"induced":[108],"death":[110,212],"while":[114],"sparing":[115],"progenitors.":[118],"Through":[119],"stable":[120],"isotope":[121],"tracing,":[122],"results":[123],"show":[124],"genetic":[126],"or":[127],"pharmacologic":[128],"truncates":[132],"tricarboxylic":[134],"acid":[135],"cycle":[136],"(TCA)":[137],"leads":[139],"anaplerotic":[141],"glutamine":[142,166,217],"metabolism":[143],"reestablish":[145],"truncated":[147],"cycle.":[148],"The":[149],"showed":[153],"divergent":[154],"fates,":[155],"as":[156,219],"lacked":[159],"plasticity":[162],"adequately":[164],"utilize":[165],"metabolism,":[167],"resulting":[168],"preferential":[170],"depletion":[171],"key":[173],"TCA":[174],"metabolites":[175],"death;":[177],"were":[180],"unaffected.":[181],"These":[182],"findings":[183],"provide":[184],"insight":[185],"into":[186,216],"mechanisms":[189],"underlie":[191],"AML's":[192],"CII.":[196],"Implications:":[197],"This":[198],"work":[199],"highlights":[200],"effects":[202],"direct":[204],"mediating":[208],"provides":[214],"insights":[215],"anaplerosis":[218],"adaptation":[222],"can":[224],"be":[225],"therapeutically":[226],"targeted.":[227]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2023-04-05T00:00:00"}