{"id":"https://openalex.org/W2969659750","doi":null,"title":"Identification of Novel Therapeutic Strategies Against MLL-rearranged Acute Lymphoblastic Leukemia in Infants","display_name":"Identification of Novel Therapeutic Strategies Against MLL-rearranged Acute Lymphoblastic Leukemia in Infants","publication_year":2019,"publication_date":"2019-09-03","ids":{"openalex":"https://openalex.org/W2969659750","mag":"2969659750"},"language":"en","primary_location":{"id":"pmh:eur:oai:repub.eur.nl:118717","doi":null,"is_oa":true,"landing_page_url":"http://hdl.handle.net/1765/118717","pdf_url":"http://hdl.handle.net/1765/118717","source":{"id":"https://openalex.org/S4377196287","display_name":"RePub (Erasmus University Rotterdam)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I913958620","host_organization_name":"Erasmus University Rotterdam","host_organization_lineage":["https://openalex.org/I913958620"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"info:eu-repo/semantics/doctoralthesis"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"http://hdl.handle.net/1765/118717","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5040836819","display_name":"Mark JB Kerstjens","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Mark Kerstjens","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5040836819"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"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/T10950","display_name":"Acute Lymphoblastic Leukemia research","score":0.9984999895095825,"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/T10950","display_name":"Acute Lymphoblastic Leukemia research","score":0.9984999895095825,"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/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.00039999998989515007,"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/T11157","display_name":"Chronic Lymphocytic Leukemia Research","score":0.00019999999494757503,"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/infant-acute-lymphoblastic-leukemia","display_name":"infant acute lymphoblastic leukemia","score":0.902999997138977},{"id":"https://openalex.org/keywords/drug-repurposing","display_name":"drug repurposing","score":0.871999979019165},{"id":"https://openalex.org/keywords/sn-38","display_name":"SN-38","score":0.843999981880188},{"id":"https://openalex.org/keywords/irinotecan","display_name":"irinotecan","score":0.9509999752044678},{"id":"https://openalex.org/keywords/topoisomerase-i-inhibitor","display_name":"topoisomerase I inhibitor","score":0.9610000252723694},{"id":"https://openalex.org/keywords/ras-mutations","display_name":"RAS mutations","score":0.9340000152587891},{"id":"https://openalex.org/keywords/mek-inhibitors","display_name":"MEK inhibitors","score":0.9869999885559082},{"id":"https://openalex.org/keywords/trametinib","display_name":"trametinib","score":0.9779999852180481},{"id":"https://openalex.org/keywords/glucocorticoid-resistance","display_name":"glucocorticoid resistance","score":0.9940000176429749},{"id":"https://openalex.org/keywords/prednisolone","display_name":"prednisolone","score":0.9679999947547913},{"id":"https://openalex.org/keywords/epigenetic-drugs","display_name":"epigenetic drugs","score":0.8500000238418579}],"concepts":[{"id":"https://openalex.org/C2909962599","wikidata":"https://www.wikidata.org/wiki/Q180664","display_name":"Lymphoblastic Leukemia","level":3,"score":0.6680022478103638},{"id":"https://openalex.org/C116834253","wikidata":"https://www.wikidata.org/wiki/Q2039217","display_name":"Identification (biology)","level":2,"score":0.5909571647644043},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4983510971069336},{"id":"https://openalex.org/C2781107101","wikidata":"https://www.wikidata.org/wiki/Q180664","display_name":"Acute lymphocytic leukemia","level":4,"score":0.47330155968666077},{"id":"https://openalex.org/C2778461978","wikidata":"https://www.wikidata.org/wiki/Q29496","display_name":"Leukemia","level":2,"score":0.4241536557674408},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.19077011942863464},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.12331748008728027},{"id":"https://openalex.org/C59822182","wikidata":"https://www.wikidata.org/wiki/Q441","display_name":"Botany","level":1,"score":0.0}],"mesh":[],"locations_count":4,"locations":[{"id":"pmh:eur:oai:repub.eur.nl:118717","doi":null,"is_oa":true,"landing_page_url":"http://hdl.handle.net/1765/118717","pdf_url":"http://hdl.handle.net/1765/118717","source":{"id":"https://openalex.org/S4377196287","display_name":"RePub (Erasmus University Rotterdam)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I913958620","host_organization_name":"Erasmus University Rotterdam","host_organization_lineage":["https://openalex.org/I913958620"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"info:eu-repo/semantics/doctoralthesis"},{"id":"pmh:oai:repub.eur.nl:118717","doi":null,"is_oa":true,"landing_page_url":"http://repub.eur.nl/pub/118717","pdf_url":"http://repub.eur.nl/pub/118717","source":{"id":"https://openalex.org/S4377196287","display_name":"RePub (Erasmus University Rotterdam)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I913958620","host_organization_name":"Erasmus University Rotterdam","host_organization_lineage":["https://openalex.org/I913958620"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"info:eu-repo/semantics/doctoralThesis"},{"id":"pmh:eur:oai:pure.eur.nl:publications/d75ad649-2684-4d51-be42-0da5127716dd","doi":null,"is_oa":true,"landing_page_url":"https://pure.eur.nl/en/publications/d75ad649-2684-4d51-be42-0da5127716dd","pdf_url":null,"source":{"id":"https://openalex.org/S4306401266","display_name":"EUR Research Repository (Erasmus University Rotterdam)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I913958620","host_organization_name":"Erasmus University Rotterdam","host_organization_lineage":["https://openalex.org/I913958620"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"info:eu-repo/semantics/doctoralthesis"},{"id":"mag:2969659750","doi":null,"is_oa":false,"landing_page_url":"https://repub.eur.nl/pub/118717/Mark-kerstjens-Complete-PDF.pdf","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":{"id":"pmh:eur:oai:repub.eur.nl:118717","doi":null,"is_oa":true,"landing_page_url":"http://hdl.handle.net/1765/118717","pdf_url":"http://hdl.handle.net/1765/118717","source":{"id":"https://openalex.org/S4377196287","display_name":"RePub (Erasmus University Rotterdam)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I913958620","host_organization_name":"Erasmus University Rotterdam","host_organization_lineage":["https://openalex.org/I913958620"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"info:eu-repo/semantics/doctoralthesis"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9922999739646912}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2969659750.pdf","grobid_xml":"https://content.openalex.org/works/W2969659750.grobid-xml"},"referenced_works_count":143,"referenced_works":["https://openalex.org/W220726306","https://openalex.org/W305459207","https://openalex.org/W313120861","https://openalex.org/W1547154484","https://openalex.org/W1549846058","https://openalex.org/W1560166507","https://openalex.org/W1584310980","https://openalex.org/W1587057944","https://openalex.org/W1605737611","https://openalex.org/W1663154925","https://openalex.org/W1757444495","https://openalex.org/W1794341310","https://openalex.org/W1801876107","https://openalex.org/W1803959510","https://openalex.org/W1817033456","https://openalex.org/W1837554294","https://openalex.org/W1912757807","https://openalex.org/W1946340684","https://openalex.org/W1965026240","https://openalex.org/W1966942042","https://openalex.org/W1968174927","https://openalex.org/W1968293348","https://openalex.org/W1972731253","https://openalex.org/W1976033223","https://openalex.org/W1976672367","https://openalex.org/W1977729188","https://openalex.org/W1981709629","https://openalex.org/W1982315838","https://openalex.org/W1982342651","https://openalex.org/W1983399286","https://openalex.org/W1985283276","https://openalex.org/W1985347144","https://openalex.org/W1985964461","https://openalex.org/W1987538151","https://openalex.org/W1988876917","https://openalex.org/W1990739246","https://openalex.org/W1997362383","https://openalex.org/W1998221028","https://openalex.org/W2002191848","https://openalex.org/W2004421253","https://openalex.org/W2005497718","https://openalex.org/W2008059340","https://openalex.org/W2011909208","https://openalex.org/W2013149980","https://openalex.org/W2014014132","https://openalex.org/W2014862318","https://openalex.org/W2017105703","https://openalex.org/W2023170820","https://openalex.org/W2023795819","https://openalex.org/W2027780027","https://openalex.org/W2033397751","https://openalex.org/W2033696561","https://openalex.org/W2036823462","https://openalex.org/W2037548653","https://openalex.org/W2039269113","https://openalex.org/W2041594420","https://openalex.org/W2044433744","https://openalex.org/W2047965845","https://openalex.org/W2053638053","https://openalex.org/W2055940669","https://openalex.org/W2061881437","https://openalex.org/W2062481845","https://openalex.org/W2063738914","https://openalex.org/W2068937934","https://openalex.org/W2069918359","https://openalex.org/W2073652391","https://openalex.org/W2076764146","https://openalex.org/W2077983342","https://openalex.org/W2078354705","https://openalex.org/W2081601480","https://openalex.org/W2081690062","https://openalex.org/W2082592723","https://openalex.org/W2086353181","https://openalex.org/W2086818132","https://openalex.org/W2087976775","https://openalex.org/W2091208410","https://openalex.org/W2092037307","https://openalex.org/W2093708765","https://openalex.org/W2094791588","https://openalex.org/W2095405591","https://openalex.org/W2096466633","https://openalex.org/W2096598682","https://openalex.org/W2098802923","https://openalex.org/W2099980194","https://openalex.org/W2100905170","https://openalex.org/W2101782876","https://openalex.org/W2101940280","https://openalex.org/W2102440338","https://openalex.org/W2103554498","https://openalex.org/W2104954848","https://openalex.org/W2108155748","https://openalex.org/W2108339680","https://openalex.org/W2113634596","https://openalex.org/W2114784462","https://openalex.org/W2115583085","https://openalex.org/W2116137191","https://openalex.org/W2119186872","https://openalex.org/W2121369158","https://openalex.org/W2124704116","https://openalex.org/W2125052019","https://openalex.org/W2125277492","https://openalex.org/W2129129812","https://openalex.org/W2129356506","https://openalex.org/W2135184154","https://openalex.org/W2135732933","https://openalex.org/W2136474966","https://openalex.org/W2139827791","https://openalex.org/W2140494950","https://openalex.org/W2141101935","https://openalex.org/W2141749176","https://openalex.org/W2141830999","https://openalex.org/W2145641334","https://openalex.org/W2147138024","https://openalex.org/W2147405665","https://openalex.org/W2151718828","https://openalex.org/W2152258603","https://openalex.org/W2154841567","https://openalex.org/W2155491820","https://openalex.org/W2156063374","https://openalex.org/W2158752749","https://openalex.org/W2164052369","https://openalex.org/W2164959344","https://openalex.org/W2166234273","https://openalex.org/W2172121723","https://openalex.org/W2172205939","https://openalex.org/W2172592582","https://openalex.org/W2211416430","https://openalex.org/W2216772862","https://openalex.org/W2261932813","https://openalex.org/W2296658645","https://openalex.org/W2302369664","https://openalex.org/W2333196452","https://openalex.org/W2336296838","https://openalex.org/W2399158532","https://openalex.org/W2413750325","https://openalex.org/W2414279676","https://openalex.org/W2436188093","https://openalex.org/W2475297214","https://openalex.org/W2508330594","https://openalex.org/W2560475455","https://openalex.org/W2725062759","https://openalex.org/W2802780965","https://openalex.org/W2952564192"],"related_works":["https://openalex.org/W3173180201","https://openalex.org/W3176501833","https://openalex.org/W2580056134","https://openalex.org/W2508330594","https://openalex.org/W7098258913","https://openalex.org/W2802780965","https://openalex.org/W2145641334","https://openalex.org/W2980090212","https://openalex.org/W2087976775","https://openalex.org/W2492309514"],"abstract_inverted_index":{"Introduction":[0],"1":[1],"patient":[2,173],"is":[3,251],"still":[4],"a":[5,78,238,323],"time-consuming":[6],"process,":[7],"especially":[8,108],"considering":[9],"the":[10,24,44,59,102,121,124,144,184,198,204,211,221,227,287,306],"fact":[11],"that":[12],"these":[13,37,292],"drugs":[14,89,271],"need":[15],"to":[16,29,57,101,210],"be":[17,27],"safe":[18],"and":[19,52,87,95,214,257,314,319],"efficacious":[20],"in":[21,55,119,130,178,222,234,237,272,283,298,309,316,326],"adults":[22],"before":[23],"transition":[25],"can":[26],"made":[28],"pediatric":[30],"application.Awaiting":[31],"results":[32,307],"from":[33],"clinical":[34],"investigation":[35,45,145],"of":[36,46,61,73,84,104,114,123,136,146,159,200,206,225,242,269,289,291],"previously":[38],"identified":[39],"therapeutics,":[40],"this":[41,74,179,310],"thesis":[42,311],"describes":[43,77],"new":[47],"therapeutic":[48,66],"candidates,":[49],"predominately":[50],"FDA-approved":[51],"off-patent":[53,88],"drugs,":[54],"order":[56],"expedite":[58],"implementation":[60],"potent":[62,112,229],"agents":[63],"into":[64],"current":[65],"regimens":[67],"for":[68],"MLLrearranged":[69,115,137,300],"infant":[70,93,116,138,246,249,281,301],"ALL.":[71],"Outline":[72],"thesisChapter":[75],"2":[76],"drug":[79,262,266],"repurposing":[80],"approach":[81],"through":[82],"screening":[83],"mainly":[85],"FDAapproved":[86],"on":[90,164,203],"different":[91,156],"MLL-rearranged":[92,149,165,207,245,248,280],"ALL":[94,117,150,208,250,282,302],"BCP-ALL":[96],"cell":[97,166],"line":[98,167],"models.This":[99],"led":[100],"identification":[103],"topoisomerase":[105],"I":[106],"inhibitors,":[107,293],"7-ethyl-10-hydroxycampthotecin":[109],"(SN-38),":[110],"as":[111,169,171,232],"inhibitors":[113,147,158,176,182,277],"cells":[118,151,209],"vitro.Additionally,":[120,284],"efficacy":[122,297],"SN-38":[125],"prodrug":[126],"irinotecan":[127],"was":[128],"investigated":[129,197,286],"vivo":[131,223],"using":[132,264],"xenograft":[133,239,303],"mouse":[134,240,304],"models":[135],"ALL.In":[139],"chapter":[140,218,235,273,317,320],"3,":[141,236],"we":[142,196,260,285],"report":[143],"against":[148],"harboring":[152],"additional":[153],"RAS":[154,189,243],"mutations.Hereto,":[155],"(approved)":[157],"RAS-pathway":[160],"components":[161],"were":[162],"tested":[163,177],"models,":[168],"well":[170],"primary":[172],"material.Among":[174],"all":[175],"study,":[180],"MEK":[181,201,230],"showed":[183],"most":[185,228],"promising":[186],"results.Moreover,":[187],"since":[188],"mutations":[190],"are":[191,312],"associated":[192],"with":[193],"glucocorticoid":[194,212],"resistance,":[195],"effect":[199],"inhibition":[202],"response":[205],"prednisolone,":[213],"observed":[215],"glucocorticoid-sensitizing":[216],"effects.Furthermore,":[217],"4":[219],"reports":[220],"evaluation":[224],"trametinib,":[226],"inhibitor":[231],"found":[233],"model":[241],"mutant":[244],"ALL.Since":[247],"characterized":[252],"by":[253],"aberrant":[254],"histone":[255],"methylation":[256],"DNA":[258],"methylation,":[259],"performed":[261],"screens":[263],"two":[265],"libraries":[267],"consisting":[268],"epigenetic":[270],"5.":[274],"S-adenosylhomocysteine":[275],"hydrolase":[276],"potently":[278],"inhibited":[279],"mechanism":[288],"action":[290],"while":[294],"also":[295],"assessing":[296],"an":[299],"model.Finally,":[305],"described":[308],"discussed":[313],"summarized":[315],"6,":[318],"7":[321],"provides":[322],"layman's":[324],"summary":[325],"Dutch.":[327]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2019-08-29T00:00:00"}