{"id":"https://openalex.org/W4362545701","doi":"https://doi.org/10.1158/2159-8290.c.6548240.v1","title":"Data from Clonal Selection with RAS Pathway Activation Mediates Secondary Clinical Resistance to Selective FLT3 Inhibition in Acute Myeloid Leukemia","display_name":"Data from Clonal Selection with RAS Pathway Activation Mediates Secondary Clinical Resistance to Selective FLT3 Inhibition in Acute Myeloid Leukemia","publication_year":2023,"publication_date":"2023-04-03","ids":{"openalex":"https://openalex.org/W4362545701","doi":"https://doi.org/10.1158/2159-8290.c.6548240.v1"},"language":"en","primary_location":{"id":"doi:10.1158/2159-8290.c.6548240.v1","doi":"https://doi.org/10.1158/2159-8290.c.6548240.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/2159-8290.c.6548240.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","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1158/2159-8290.c.6548240.v1","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5068824166","display_name":"Christine M. McMahon","orcid":"https://orcid.org/0000-0001-9745-9595","observed_orcids":["https://orcid.org/0000-0001-9745-9595"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Christine M. McMahon","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056322810","display_name":"Timothy T. Ferng","orcid":"https://orcid.org/0000-0002-1784-2656","observed_orcids":["https://orcid.org/0000-0002-1784-2656"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Timothy Ferng","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5037018787","display_name":"Jonathan Canaani","orcid":"https://orcid.org/0000-0002-5294-3524","observed_orcids":["https://orcid.org/0000-0002-5294-3524"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jonathan Canaani","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5038660651","display_name":"Eunice S. Wang","orcid":"https://orcid.org/0000-0002-8644-0968","observed_orcids":["https://orcid.org/0000-0002-8644-0968"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Eunice S. Wang","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029451307","display_name":"Jennifer J. D. Morrissette","orcid":"https://orcid.org/0000-0001-9460-7177","observed_orcids":["https://orcid.org/0000-0001-9460-7177"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jennifer J.D. Morrissette","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0001-9460-7177","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5062145996","display_name":"Dennis J. Eastburn","orcid":"https://orcid.org/0009-0003-1514-5544","observed_orcids":["https://orcid.org/0009-0003-1514-5544"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Dennis J. Eastburn","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002798041","display_name":"Maurizio Pellegrino","orcid":"https://orcid.org/0000-0002-2838-2157","observed_orcids":["https://orcid.org/0000-0002-2838-2157"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Maurizio Pellegrino","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-2838-2157","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5013504740","display_name":"Robert Durruthy-Durruthy","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Robert Durruthy-Durruthy","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014940800","display_name":"Christopher D. Watt","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Christopher D. Watt","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002785726","display_name":"Saurabh Asthana","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Saurabh Asthana","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025596379","display_name":"Elisabeth A. Lasater","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Elisabeth A. Lasater","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014067753","display_name":"RosaAnna DeFilippis","orcid":"https://orcid.org/0009-0006-1365-235X","observed_orcids":["https://orcid.org/0009-0006-1365-235X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"RosaAnna DeFilippis","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034417710","display_name":"Cheryl A.C. Peretz","orcid":"https://orcid.org/0000-0002-0855-6770","observed_orcids":["https://orcid.org/0000-0002-0855-6770"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Cheryl A.C. Peretz","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5068488176","display_name":"Lisa H.F. McGary","orcid":"https://orcid.org/0000-0001-6473-1177","observed_orcids":["https://orcid.org/0000-0001-6473-1177"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Lisa H.F. McGary","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5076640752","display_name":"Safoora Deihimi","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Safoora Deihimi","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5071733656","display_name":"Aaron C. Logan","orcid":"https://orcid.org/0000-0002-1179-5879","observed_orcids":["https://orcid.org/0000-0002-1179-5879"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Aaron C. Logan","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014838335","display_name":"Selina M. Luger","orcid":"https://orcid.org/0000-0003-3364-4366","observed_orcids":["https://orcid.org/0000-0003-3364-4366"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Selina M. Luger","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5015115182","display_name":"Neil P. Shah","orcid":"https://orcid.org/0000-0003-4398-3388","observed_orcids":["https://orcid.org/0000-0003-4398-3388"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Neil P. Shah","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5032477226","display_name":"Martin P Carroll","orcid":"https://orcid.org/0000-0002-5622-3735","observed_orcids":["https://orcid.org/0000-0002-5622-3735"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Martin Carroll","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5091814150","display_name":"Catherine Choy Smith","orcid":"https://orcid.org/0000-0003-0160-7026","observed_orcids":["https://orcid.org/0000-0003-0160-7026"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Catherine C. Smith","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5037460404","display_name":"Alexander E. Perl","orcid":"https://orcid.org/0000-0002-1463-2231","observed_orcids":["https://orcid.org/0000-0002-1463-2231"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Alexander E. Perl","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-1463-2231","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/T10309","display_name":"Acute Myeloid Leukemia Research","score":1.0,"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":1.0,"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/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.0,"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/T11215","display_name":"Chronic Myeloid Leukemia Treatments","score":0.0,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/acute-myeloid-leukemia","display_name":"acute myeloid leukemia","score":0.9559999704360962},{"id":"https://openalex.org/keywords/flt3-mutation","display_name":"FLT3 mutation","score":0.7020000219345093},{"id":"https://openalex.org/keywords/gilteritinib","display_name":"gilteritinib","score":0.9919999837875366},{"id":"https://openalex.org/keywords/flt3-inhibitor-resistance","display_name":"FLT3 inhibitor resistance","score":0.7289999723434448},{"id":"https://openalex.org/keywords/nras-mutation","display_name":"NRAS mutation","score":0.675000011920929},{"id":"https://openalex.org/keywords/kras-mutation","display_name":"KRAS mutation","score":1.0},{"id":"https://openalex.org/keywords/clonal-selection","display_name":"clonal selection","score":0.8019999861717224},{"id":"https://openalex.org/keywords/clonal-evolution","display_name":"clonal evolution","score":0.921999990940094},{"id":"https://openalex.org/keywords/bcr-abl-fusion","display_name":"BCR-ABL fusion gene","score":0.8059999942779541},{"id":"https://openalex.org/keywords/tyrosine-kinase-inhibitor-resistance","display_name":"tyrosine kinase inhibitor resistance","score":0.8949999809265137},{"id":"https://openalex.org/keywords/relapsed-refractory-aml","display_name":"relapsed/refractory AML","score":0.765999972820282},{"id":"https://openalex.org/keywords/single-cell-dna-sequencing","display_name":"single-cell DNA sequencing","score":0.6679999828338623},{"id":"https://openalex.org/keywords/targeted-next-generation-sequencing","display_name":"targeted next-generation sequencing","score":0.6209999918937683}],"concepts":[{"id":"https://openalex.org/C21790070","wikidata":"https://www.wikidata.org/wiki/Q18030215","display_name":"Neuroblastoma RAS viral oncogene homolog","level":5,"score":0.7115990519523621},{"id":"https://openalex.org/C2781187634","wikidata":"https://www.wikidata.org/wiki/Q20969980","display_name":"KRAS","level":4,"score":0.6312713623046875},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5785451531410217},{"id":"https://openalex.org/C113968399","wikidata":"https://www.wikidata.org/wiki/Q7559241","display_name":"Somatic evolution in cancer","level":3,"score":0.5401408076286316},{"id":"https://openalex.org/C2778729363","wikidata":"https://www.wikidata.org/wiki/Q11688946","display_name":"Myeloid leukemia","level":2,"score":0.5298842191696167},{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.48906904458999634},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4688490629196167},{"id":"https://openalex.org/C2779282312","wikidata":"https://www.wikidata.org/wiki/Q1956561","display_name":"Myeloid","level":2,"score":0.4344882369041443},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.4059829115867615},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.3344663381576538},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.15882432460784912},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.13317236304283142},{"id":"https://openalex.org/C151730666","wikidata":"https://www.wikidata.org/wiki/Q7205","display_name":"Paleontology","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/2159-8290.c.6548240.v1","doi":"https://doi.org/10.1158/2159-8290.c.6548240.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/2159-8290.c.6548240.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:10.1158/2159-8290.c.6548240.v1","doi":"https://doi.org/10.1158/2159-8290.c.6548240.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/2159-8290.c.6548240.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":0.9391000270843506}],"sustainable_development_goals_aurora":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.5099999904632568}],"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/W2266896604","https://openalex.org/W2315043173","https://openalex.org/W2603968999","https://openalex.org/W2029503777","https://openalex.org/W4242147590","https://openalex.org/W2730247823","https://openalex.org/W2997573493","https://openalex.org/W4382806856","https://openalex.org/W3159338278","https://openalex.org/W2693067620"],"abstract_inverted_index":{"Abstract":[0],"Gilteritinib":[1],"is":[2,26,32,215],"a":[3],"potent":[4],"and":[5,29,47,106,137,145,179,209],"selective":[6,167],"FLT3":[7,111,127,168],"kinase":[8,150,186],"inhibitor":[9,151,169],"with":[10,165],"single-agent":[11],"clinical":[12,54,182],"efficacy":[13],"in":[14,79,108,119,140,153,188,217],"relapsed/refractory":[15],"FLT3-mutated":[16,120,189],"acute":[17],"myeloid":[18],"leukemia":[19],"(AML).":[20],"In":[21,219],"this":[22],"context,":[23],"however,":[24],"gilteritinib":[25,68,170],"not":[27],"curative,":[28],"response":[30,109,144],"duration":[31],"limited":[33],"by":[34,207],"the":[35,62,114,122,166,194,218],"development":[36,195],"of":[37,56,64,103,116,124,159,176,196],"secondary":[38,85],"resistance.":[39],"To":[40],"evaluate":[41],"resistance":[42,146,183],"mechanisms,":[43],"we":[44],"analyzed":[45],"baseline":[46],"progression":[48,66],"samples":[49],"from":[50,162],"patients":[51,163],"treated":[52,164],"on":[53,67],"trials":[55],"gilteritinib.":[57],"Targeted":[58],"next-generation":[59],"sequencing":[60,99],"at":[61,94],"time":[63],"AML":[65,160],"identified":[69,93],"treatment-emergent":[70],"mutations":[71,88,118],"that":[72,172],"activate":[73],"RAS/MAPK":[74],"pathway":[75],"signaling,":[76],"most":[77],"commonly":[78],"NRAS":[80],"or":[81,89,129],"KRAS.":[82],"Less":[83],"frequently,":[84],"FLT3-F691L":[86],"gatekeeper":[87],"BCR\u2013ABL1":[90],"fusions":[91],"were":[92],"progression.":[95],"Single-cell":[96],"targeted":[97,198],"DNA":[98],"revealed":[100],"diverse":[101],"patterns":[102,131,175],"clonal":[104,141,177],"selection":[105,178],"evolution":[107,180],"to":[110,147,184],"inhibition,":[112],"including":[113],"emergence":[115],"RAS":[117],"subclones,":[121,128],"expansion":[123],"alternative":[125],"wild-type":[126],"both":[130],"simultaneously.":[132],"These":[133],"data":[134,192],"illustrate":[135],"dynamic":[136],"complex":[138],"changes":[139],"architecture":[142],"underlying":[143],"mutation-selective":[148],"tyrosine":[149,185],"therapy":[152],"AML.":[154,190,203],"Significance:":[155],"Comprehensive":[156],"serial":[157],"genotyping":[158],"specimens":[161],"demonstrates":[171],"complex,":[173],"heterogeneous":[174],"mediate":[181],"inhibition":[187],"Our":[191],"support":[193],"combinatorial":[197],"therapeutic":[199],"approaches":[200],"for":[201],"advanced":[202],"See":[204],"related":[205],"commentary":[206],"Wei":[208],"Roberts,":[210],"p.":[211,223],"998.":[212],"This":[213,220],"article":[214],"highlighted":[216],"Issue":[221],"feature,":[222],"983":[224]},"counts_by_year":[],"updated_date":"2026-09-25T08:18:29.962427","created_date":"2025-10-10T00:00:00"}