{"id":"https://openalex.org/W4379984252","doi":"https://doi.org/10.1158/1538-7445.am2023-6625","title":"Abstract 6625: Mathematical modeling of single-cell data reveals the key role of stochasticity - not fitness - in determining the clonal origins of relapse in childhood leukemia","display_name":"Abstract 6625: Mathematical modeling of single-cell data reveals the key role of stochasticity - not fitness - in determining the clonal origins of relapse in childhood leukemia","publication_year":2023,"publication_date":"2023-04-04","ids":{"openalex":"https://openalex.org/W4379984252","doi":"https://doi.org/10.1158/1538-7445.am2023-6625"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2023-6625","doi":"https://doi.org/10.1158/1538-7445.am2023-6625","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.am2023-6625","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"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/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","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/A5025292471","display_name":"Virginia A. Turati","orcid":"https://orcid.org/0000-0002-1013-9490","observed_orcids":["https://orcid.org/0000-0002-1013-9490"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Virginia Turati","raw_affiliation_strings":["1H. Lee Moffitt Cancer Center, Tampa, FL;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1H. Lee Moffitt Cancer Center, Tampa, FL;","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5048365807","display_name":"Javier Herrero","orcid":"https://orcid.org/0000-0001-7313-717X","observed_orcids":["https://orcid.org/0000-0001-7313-717X"]},"institutions":[{"id":"https://openalex.org/I45129253","display_name":"University College London","ror":"https://ror.org/02jx3x895","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I45129253"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Javier Herrero","raw_affiliation_strings":["2University College London, London, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2University College London, London, United Kingdom","institution_ids":["https://openalex.org/I45129253"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074607695","display_name":"Mark Robertson\u2010Tessi","orcid":"https://orcid.org/0000-0003-0143-9587","observed_orcids":["https://orcid.org/0000-0003-0143-9587"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mark Robertson-Tessi","raw_affiliation_strings":["1H. Lee Moffitt Cancer Center, Tampa, FL;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1H. Lee Moffitt Cancer Center, Tampa, FL;","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5059661708","display_name":"Tariq Enver","orcid":"https://orcid.org/0000-0002-0866-6443","observed_orcids":["https://orcid.org/0000-0002-0866-6443"]},"institutions":[{"id":"https://openalex.org/I45129253","display_name":"University College London","ror":"https://ror.org/02jx3x895","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I45129253"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Tariq Enver","raw_affiliation_strings":["2University College London, London, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2University College London, London, United Kingdom","institution_ids":["https://openalex.org/I45129253"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009118439","display_name":"Andriy Marusyk","orcid":"https://orcid.org/0000-0002-0087-9575","observed_orcids":["https://orcid.org/0000-0002-0087-9575"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Andriy Marusyk","raw_affiliation_strings":["1H. Lee Moffitt Cancer Center, Tampa, FL;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1H. Lee Moffitt Cancer Center, Tampa, FL;","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5069501174","display_name":"Alexander R.A. Anderson","orcid":"https://orcid.org/0000-0002-2536-4383","observed_orcids":["https://orcid.org/0000-0002-2536-4383"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Alexander RA Anderson","raw_affiliation_strings":["1H. Lee Moffitt Cancer Center, Tampa, FL;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1H. Lee Moffitt Cancer Center, Tampa, FL;","institution_ids":["https://openalex.org/I3019308854"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":2,"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":"83","issue":"7_Supplement","first_page":"6625","last_page":"6625"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10950","display_name":"Acute Lymphoblastic Leukemia research","score":0.9696999788284302,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"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/T10950","display_name":"Acute Lymphoblastic Leukemia research","score":0.9696999788284302,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"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":0.014999999664723873,"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/T11829","display_name":"Mathematical Biology Tumor Growth","score":0.00430000014603138,"subfield":{"id":"https://openalex.org/subfields/2611","display_name":"Modeling and Simulation"},"field":{"id":"https://openalex.org/fields/26","display_name":"Mathematics"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/childhood-acute-lymphoblastic-leukemia","display_name":"childhood acute lymphoblastic leukemia","score":0.8790000081062317},{"id":"https://openalex.org/keywords/relapse","display_name":"relapse","score":0.7009999752044678},{"id":"https://openalex.org/keywords/clonal-evolution","display_name":"clonal evolution","score":0.890999972820282},{"id":"https://openalex.org/keywords/clonal-dominance","display_name":"clonal dominance","score":0.75},{"id":"https://openalex.org/keywords/clonal-fitness","display_name":"clonal fitness","score":0.9580000042915344},{"id":"https://openalex.org/keywords/agent-based-modeling","display_name":"agent-based modeling","score":0.6259999871253967},{"id":"https://openalex.org/keywords/mathematical-modeling","display_name":"mathematical modeling","score":0.7200000286102295},{"id":"https://openalex.org/keywords/single-cell-genomics","display_name":"single-cell genomics","score":0.6420000195503235},{"id":"https://openalex.org/keywords/residual-disease","display_name":"residual disease","score":0.4959999918937683},{"id":"https://openalex.org/keywords/quiescence","display_name":"quiescence","score":0.6589999794960022},{"id":"https://openalex.org/keywords/founder-effect","display_name":"founder effect","score":0.8429999947547913},{"id":"https://openalex.org/keywords/clonal-heterogeneity","display_name":"clonal heterogeneity","score":0.5920000076293945},{"id":"https://openalex.org/keywords/xenografts","display_name":"xenografts","score":0.5490000247955322},{"id":"https://openalex.org/keywords/treatment-resistance","display_name":"treatment resistance","score":0.38499999046325684}],"concepts":[{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.7292048335075378},{"id":"https://openalex.org/C2908647359","wikidata":"https://www.wikidata.org/wiki/Q2625603","display_name":"Population","level":2,"score":0.5376689434051514},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.4609639346599579},{"id":"https://openalex.org/C2778461978","wikidata":"https://www.wikidata.org/wiki/Q29496","display_name":"Leukemia","level":2,"score":0.4422208070755005},{"id":"https://openalex.org/C2993561819","wikidata":"https://www.wikidata.org/wiki/Q5097977","display_name":"Pediatric cancer","level":3,"score":0.43147727847099304},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4266173839569092},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3467696011066437},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.34272149205207825},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.3414246737957001},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.225666344165802},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.21529453992843628},{"id":"https://openalex.org/C99454951","wikidata":"https://www.wikidata.org/wiki/Q932068","display_name":"Environmental health","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2023-6625","doi":"https://doi.org/10.1158/1538-7445.am2023-6625","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.am2023-6625","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"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/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9391000270843506,"display_name":"Good health and well-being"}],"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/W4280537932","https://openalex.org/W2784875453","https://openalex.org/W2750144336","https://openalex.org/W4310273904","https://openalex.org/W54791039","https://openalex.org/W2980436354","https://openalex.org/W2159884655","https://openalex.org/W2060383229","https://openalex.org/W2405478812","https://openalex.org/W2891906852"],"abstract_inverted_index":{"Abstract":[0],"Acute":[1],"lymphoblastic":[2],"leukemia":[3,332,452],"(cALL)":[4],"is":[5,114,274],"the":[6,25,33,37,41,93,104,130,150,205,228,234,252,259,280,302,330,357,366,377,387,391,399,434,445,457],"most":[7,309],"common":[8],"pediatric":[9],"cancer,":[10],"and":[11,67,121,148,153,177,184,189,207,258,371,406,469],"since":[12],"up":[13],"to":[14,22,46,92,119,163,196,220,251,266,291,376],"20%":[15],"of":[16,28,62,76,87,111,157,204,210,254,261,271,296,301,329,368,381,390,430,437,448,456],"children":[17],"relapse":[18,47,314,392,449],"after":[19,190],"initially":[20,360],"responding":[21],"chemotherapy":[23],"treatment,":[24],"largest":[26],"cause":[27],"cancer-related":[29],"childhood":[30,451],"deaths":[31],"in":[32,99,172,224,229,248,308,323,443,450],"western":[34],"world.":[35],"With":[36],"idea":[38],"that":[39,71,96],"dissecting":[40],"evolutionary":[42,89,155],"population":[43],"dynamics":[44,131,295],"leading":[45,91],"would":[48],"help":[49],"explain":[50],"treatment":[51,97,217,239,282,328,411],"failure":[52],"from":[53,161,182,316,384],"a":[54,81,108,288,342,351,372],"mechanistic":[55],"standpoint,":[56],"several":[57,241,297],"studies":[58,113],"have":[59,166],"performed":[60],"comparisons":[61],"genetic":[63,393],"heterogeneity":[64],"at":[65,103,313],"diagnosis":[66,162],"relapse.":[68],"These":[69,192],"showed":[70,305],"as":[72,74],"many":[73],"70%":[75],"relapses":[77],"are":[78,135],"dominated":[79],"by":[80],"single":[82],"diagnostic":[83],"subclone":[84],"or":[85,350],"one":[86],"its":[88],"progeny;":[90],"prevailing":[94],"view":[95],"selection":[98],"cALL":[100,159,238],"primarily":[101,118],"operates":[102],"genotype":[105,206,364],"level.":[106],"However,":[107,277],"crucial":[109],"caveat":[110],"these":[112],"their":[115],"reliance,":[116],"due":[117],"technical":[120],"economic":[122],"constraints,":[123],"on":[124,139,279],"very":[125],"limited":[126],"data":[127,146,169,179,304,397,432],"timepoints.":[128],"While":[129],"linking":[132],"said":[133],"timepoints":[134],"often":[136],"interpreted":[137],"based":[138,278],"simple":[140],"intuition.":[141],"To":[142],"overcome":[143],"this":[144],"sparse":[145],"challenge":[147],"reconstruct":[149],"entire":[151],"spatial":[152],"temporal":[154],"trajectories":[156],"individual":[158,211,382],"cells":[160,187,212,257,383],"relapse,":[164],"we":[165,222],"integrated":[167],"experimental":[168,235],"with":[170,333,341,356,403],"an":[171,198,334],"silico":[173,230],"model.":[174],"Single-cell":[175],"WGS":[176],"RNAseq":[178],"were":[180,193,226,386],"obtained":[181],"primary":[183],"xenografted":[185],"leukemic":[186],"before":[188],"chemotherapy.":[191],"then":[194],"used":[195],"parameterize":[197],"agent-based":[199],"mathematical":[200],"model":[201,231,286],"allowing":[202],"tracking":[203],"evolving":[208],"phenotype":[209],"over":[213],"time.":[214],"When":[215],"short":[216],"courses":[218],"akin":[219],"those":[221],"delivered":[223],"vivo":[225],"used,":[227],"closely":[232],"recapitulated":[233],"results.":[236],"Since":[237],"lasts":[240],"years,":[242],"it":[243],"cannot":[244],"be":[245],"entirely":[246],"modelled":[247],"vivo.":[249],"Due":[250],"rarity":[253],"post-treatment":[255],"residual":[256,369],"lack":[260],"universal":[262],"cell":[263],"surface":[264],"markers":[265],"isolate":[267],"them,":[268],"direct":[269],"analysis":[270,300,405],"clinical":[272],"samples":[273],"also":[275],"challenging.":[276],"initial":[281],"data,":[283],"our":[284,396],"calibrated":[285],"provided":[287],"unique":[289],"opportunity":[290],"simulate":[292],"longer":[293],"remission-relapse":[294],"leukemias.":[298],"Mechanistic":[299],"collected":[303],"that,":[306],"strikingly,":[307],"cases,":[310],"clonal":[311,324,345,446],"dominance":[312],"results":[315],"stochastic":[317,378],"sweeps":[318],"rather":[319],"than":[320,355,363],"deterministic":[321],"differences":[322],"fitness.":[325],"Indeed,":[326],"independent":[327],"same":[331,358],"identical":[335],"drug":[336],"regimen":[337],"more":[338],"frequently":[339],"ended":[340],"considerably":[343],"different":[344,352],"landscape":[346],"(either":[347],"polyclonal":[348],"disease":[349,370],"dominant":[353],"clone)":[354],"outcome":[359],"observed.":[361],"Rather":[362],"differences,":[365],"size":[367],"founder":[373],"effect":[374],"linked":[375],"exit,":[379],"post-treatment,":[380],"quiescence":[385],"key":[388,435],"determinants":[389],"landscape.":[394],"Altogether,":[395],"highlight":[398],"misinterpretation":[400],"risk":[401],"associated":[402],"snapshot":[404],"might":[407],"inform":[408],"promising":[409],"alternative":[410],"schedules.":[412],"Citation":[413],"Format:":[414],"Virginia":[415],"Turati,":[416],"Javier":[417],"Herrero,":[418],"Mark":[419],"Robertson-Tessi,":[420],"Tariq":[421],"Enver,":[422],"Andriy":[423],"Marusyk,":[424],"Alexander":[425],"RA":[426],"Anderson.":[427],"Mathematical":[428],"modeling":[429],"single-cell":[431],"reveals":[433],"role":[436],"stochasticity":[438],"-":[439,442],"not":[440],"fitness":[441],"determining":[444],"origins":[447],"[abstract].":[453],"In:":[454],"Proceedings":[455],"American":[458],"Association":[459],"for":[460],"Cancer":[461,480],"Research":[462],"Annual":[463],"Meeting":[464],"2023;":[465],"Part":[466],"1":[467],"(Regular":[468],"Invited":[470],"Abstracts);":[471],"2023":[472],"Apr":[473],"14-19;":[474],"Orlando,":[475],"FL.":[476],"Philadelphia":[477],"(PA):":[478],"AACR;":[479],"Res":[481],"2023;83(7_Suppl):Abstract":[482],"nr":[483],"6625.":[484]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2023-06-10T00:00:00"}