{"id":"https://openalex.org/W2979882802","doi":"https://doi.org/10.1182/blood.v128.22.3514.3514","title":"Pacritinib Targets IRAK1 and Shows Synergy with HDAC and BET Inhibitors in Acute Myeloid Leukemia","display_name":"Pacritinib Targets IRAK1 and Shows Synergy with HDAC and BET Inhibitors in Acute Myeloid Leukemia","publication_year":2016,"publication_date":"2016-12-02","ids":{"openalex":"https://openalex.org/W2979882802","doi":"https://doi.org/10.1182/blood.v128.22.3514.3514","mag":"2979882802"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v128.22.3514.3514","doi":"https://doi.org/10.1182/blood.v128.22.3514.3514","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v128.22.3514.3514","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/A5041816421","display_name":"Alka Puri","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I165690674","display_name":"Oregon Health & Science University","ror":"https://ror.org/009avj582","country_code":"US","type":"education","lineage":["https://openalex.org/I165690674"]},{"id":"https://openalex.org/I4390039369","display_name":"OHSU Knight Cancer Institute","ror":"https://ror.org/002shna07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Alka Puri","raw_affiliation_strings":["Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR","institution_ids":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5065432367","display_name":"Shawn Mahmood","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I165690674","display_name":"Oregon Health & Science University","ror":"https://ror.org/009avj582","country_code":"US","type":"education","lineage":["https://openalex.org/I165690674"]},{"id":"https://openalex.org/I4390039369","display_name":"OHSU Knight Cancer Institute","ror":"https://ror.org/002shna07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Shawn Mahmood","raw_affiliation_strings":["Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR","institution_ids":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5054919076","display_name":"Bernadette Maertens","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I165690674","display_name":"Oregon Health & Science University","ror":"https://ror.org/009avj582","country_code":"US","type":"education","lineage":["https://openalex.org/I165690674"]},{"id":"https://openalex.org/I4390039369","display_name":"OHSU Knight Cancer Institute","ror":"https://ror.org/002shna07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Bernadette Maertens","raw_affiliation_strings":["Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR","institution_ids":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045185741","display_name":"Monika Ashok Davare","orcid":"https://orcid.org/0000-0003-1802-7597","observed_orcids":["https://orcid.org/0000-0003-1802-7597"]},"institutions":[{"id":"https://openalex.org/I165690674","display_name":"Oregon Health & Science University","ror":"https://ror.org/009avj582","country_code":"US","type":"education","lineage":["https://openalex.org/I165690674"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Monika Davare","raw_affiliation_strings":["Pap\u00e9 Pediatric Research Institute, Department of Pediatrics, Oregon Health & Science University, Portland, OR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pap\u00e9 Pediatric Research Institute, Department of Pediatrics, Oregon Health & Science University, Portland, OR","institution_ids":["https://openalex.org/I165690674"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5075070858","display_name":"Stephen E. Kurtz","orcid":"https://orcid.org/0000-0003-4762-389X","observed_orcids":["https://orcid.org/0000-0003-4762-389X"]},"institutions":[{"id":"https://openalex.org/I165690674","display_name":"Oregon Health & Science University","ror":"https://ror.org/009avj582","country_code":"US","type":"education","lineage":["https://openalex.org/I165690674"]},{"id":"https://openalex.org/I4390039369","display_name":"OHSU Knight Cancer Institute","ror":"https://ror.org/002shna07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Stephen E Kurtz","raw_affiliation_strings":["Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR","institution_ids":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014545118","display_name":"Cristina E. Tognon","orcid":"https://orcid.org/0000-0002-4872-3078","observed_orcids":["https://orcid.org/0000-0002-4872-3078"]},"institutions":[{"id":"https://openalex.org/I1344073410","display_name":"Howard Hughes Medical Institute","ror":"https://ror.org/006w34k90","country_code":"US","type":"facility","lineage":["https://openalex.org/I1344073410"]},{"id":"https://openalex.org/I165690674","display_name":"Oregon Health & Science University","ror":"https://ror.org/009avj582","country_code":"US","type":"education","lineage":["https://openalex.org/I165690674"]},{"id":"https://openalex.org/I4390039369","display_name":"OHSU Knight Cancer Institute","ror":"https://ror.org/002shna07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Cristina E. Tognon","raw_affiliation_strings":["Howard Hughes Medical Institute, Portland, OR","Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Howard Hughes Medical Institute, Portland, OR","institution_ids":["https://openalex.org/I1344073410"]},{"raw_affiliation_string":"Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR","institution_ids":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008775668","display_name":"Christopher O. Eden","orcid":"https://orcid.org/0000-0002-1465-8693","observed_orcids":["https://orcid.org/0000-0002-1465-8693"]},"institutions":[{"id":"https://openalex.org/I165690674","display_name":"Oregon Health & Science University","ror":"https://ror.org/009avj582","country_code":"US","type":"education","lineage":["https://openalex.org/I165690674"]},{"id":"https://openalex.org/I4390039369","display_name":"OHSU Knight Cancer Institute","ror":"https://ror.org/002shna07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Christopher O. Eden","raw_affiliation_strings":["Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR","institution_ids":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5037294253","display_name":"Johannes Elferich","orcid":"https://orcid.org/0000-0002-9911-706X","observed_orcids":["https://orcid.org/0000-0002-9911-706X"]},"institutions":[{"id":"https://openalex.org/I165690674","display_name":"Oregon Health & Science University","ror":"https://ror.org/009avj582","country_code":"US","type":"education","lineage":["https://openalex.org/I165690674"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Johannes Elferich","raw_affiliation_strings":["Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR","institution_ids":["https://openalex.org/I165690674"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066661471","display_name":"Ujwal P. Shinde","orcid":"https://orcid.org/0000-0001-6229-2609","observed_orcids":["https://orcid.org/0000-0001-6229-2609"]},"institutions":[{"id":"https://openalex.org/I165690674","display_name":"Oregon Health & Science University","ror":"https://ror.org/009avj582","country_code":"US","type":"education","lineage":["https://openalex.org/I165690674"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ujwal Shinde","raw_affiliation_strings":["Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR","institution_ids":["https://openalex.org/I165690674"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5125591963","display_name":"Brian J. Druker","orcid":"https://orcid.org/0000-0001-8331-8206","observed_orcids":["https://orcid.org/0000-0001-8331-8206"]},"institutions":[{"id":"https://openalex.org/I1344073410","display_name":"Howard Hughes Medical Institute","ror":"https://ror.org/006w34k90","country_code":"US","type":"facility","lineage":["https://openalex.org/I1344073410"]},{"id":"https://openalex.org/I165690674","display_name":"Oregon Health & Science University","ror":"https://ror.org/009avj582","country_code":"US","type":"education","lineage":["https://openalex.org/I165690674"]},{"id":"https://openalex.org/I4390039369","display_name":"OHSU Knight Cancer Institute","ror":"https://ror.org/002shna07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Brian J. Druker","raw_affiliation_strings":["Howard Hughes Medical Institute, Portland, OR","Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Howard Hughes Medical Institute, Portland, OR","institution_ids":["https://openalex.org/I1344073410"]},{"raw_affiliation_string":"Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR","institution_ids":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5071375525","display_name":"Jack W. Singer","orcid":"https://orcid.org/0000-0003-4001-4549","observed_orcids":["https://orcid.org/0000-0003-4001-4549"]},"institutions":[{"id":"https://openalex.org/I4210101701","display_name":"CTI BioPharma (United States)","ror":"https://ror.org/017bk0e71","country_code":"US","type":"company","lineage":["https://openalex.org/I4210101701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jack W. Singer","raw_affiliation_strings":["CTI BioPharma Corp., Seattle, WA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"CTI BioPharma Corp., Seattle, WA","institution_ids":["https://openalex.org/I4210101701"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5076074507","display_name":"Anupriya Agarwal","orcid":"https://orcid.org/0000-0002-8319-6162","observed_orcids":["https://orcid.org/0000-0002-8319-6162"]},"institutions":[{"id":"https://openalex.org/I165690674","display_name":"Oregon Health & Science University","ror":"https://ror.org/009avj582","country_code":"US","type":"education","lineage":["https://openalex.org/I165690674"]},{"id":"https://openalex.org/I4390039369","display_name":"OHSU Knight Cancer Institute","ror":"https://ror.org/002shna07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Anupriya Agarwal","raw_affiliation_strings":["Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR","institution_ids":["https://openalex.org/I165690674","https://openalex.org/I4390039369"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":0.3165,"has_fulltext":false,"cited_by_count":3,"citation_normalized_percentile":{"value":0.73020816,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":94},"biblio":{"volume":"128","issue":"22","first_page":"3514","last_page":"3514"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.9994999766349792,"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":0.9994999766349792,"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/T11559","display_name":"Retinoids in leukemia and cellular processes","score":9.999999747378752e-05,"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"}},{"id":"https://openalex.org/T12534","display_name":"Protein Degradation and Inhibitors","score":0.0,"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/pacritinib","display_name":"pacritinib","score":0.9789999723434448},{"id":"https://openalex.org/keywords/irak1","display_name":"IRAK1","score":0.9670000076293945},{"id":"https://openalex.org/keywords/acute-myeloid-leukemia","display_name":"acute myeloid leukemia","score":0.9990000128746033},{"id":"https://openalex.org/keywords/il-1-signaling","display_name":"IL-1 signaling","score":0.9539999961853027},{"id":"https://openalex.org/keywords/drug-synergy","display_name":"drug synergy","score":0.5370000004768372},{"id":"https://openalex.org/keywords/histone-deacetylase-inhibitors","display_name":"histone deacetylase inhibitors","score":0.9160000085830688},{"id":"https://openalex.org/keywords/bet-inhibitors","display_name":"BET inhibitors","score":0.9900000095367432},{"id":"https://openalex.org/keywords/bruton-tyrosine-kinase-inhibitors","display_name":"BTK inhibitors","score":0.6869999766349792},{"id":"https://openalex.org/keywords/bh3-mimetics","display_name":"BH3 mimetics","score":0.9660000205039978},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.7400000095367432},{"id":"https://openalex.org/keywords/bone-marrow-microenvironment","display_name":"bone marrow microenvironment","score":0.8429999947547913},{"id":"https://openalex.org/keywords/kinase-inhibitor-selectivity","display_name":"kinase selectivity","score":0.5460000038146973},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.7580000162124634}],"concepts":[{"id":"https://openalex.org/C54174078","wikidata":"https://www.wikidata.org/wiki/Q3197188","display_name":"Kinome","level":3,"score":0.7775932550430298},{"id":"https://openalex.org/C2778729363","wikidata":"https://www.wikidata.org/wiki/Q11688946","display_name":"Myeloid leukemia","level":2,"score":0.6440539360046387},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.624247670173645},{"id":"https://openalex.org/C2780862049","wikidata":"https://www.wikidata.org/wiki/Q25326844","display_name":"BET inhibitor","level":5,"score":0.5424157381057739},{"id":"https://openalex.org/C2776112149","wikidata":"https://www.wikidata.org/wiki/Q7383611","display_name":"Ruxolitinib","level":4,"score":0.5102198123931885},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.4503931403160095},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.4405028820037842},{"id":"https://openalex.org/C2778461978","wikidata":"https://www.wikidata.org/wiki/Q29496","display_name":"Leukemia","level":2,"score":0.42897704243659973},{"id":"https://openalex.org/C2779282312","wikidata":"https://www.wikidata.org/wiki/Q1956561","display_name":"Myeloid","level":2,"score":0.42627331614494324},{"id":"https://openalex.org/C2778305200","wikidata":"https://www.wikidata.org/wiki/Q174378","display_name":"Histone deacetylase","level":4,"score":0.421773225069046},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.40580880641937256},{"id":"https://openalex.org/C74401373","wikidata":"https://www.wikidata.org/wiki/Q1829843","display_name":"Bromodomain","level":4,"score":0.35409143567085266},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3153473138809204},{"id":"https://openalex.org/C2780076729","wikidata":"https://www.wikidata.org/wiki/Q1752571","display_name":"Myelofibrosis","level":3,"score":0.23550188541412354},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.2303638458251953},{"id":"https://openalex.org/C2780007613","wikidata":"https://www.wikidata.org/wiki/Q546523","display_name":"Bone marrow","level":2,"score":0.20447653532028198},{"id":"https://openalex.org/C64927066","wikidata":"https://www.wikidata.org/wiki/Q36293","display_name":"Histone","level":3,"score":0.1733483374118805},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.11356785893440247},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.096774160861969},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.07623660564422607}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v128.22.3514.3514","doi":"https://doi.org/10.1182/blood.v128.22.3514.3514","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v128.22.3514.3514","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":[{"id":"https://metadata.un.org/sdg/3","score":0.9537000060081482,"display_name":"Good health and well-being"}],"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/W2979608637","https://openalex.org/W2794827287","https://openalex.org/W2043124942","https://openalex.org/W1981229807","https://openalex.org/W2218417427","https://openalex.org/W2946601400","https://openalex.org/W2164145660","https://openalex.org/W2554484272","https://openalex.org/W7051994074","https://openalex.org/W4389235237"],"abstract_inverted_index":{"Abstract":[0],"Background:":[1],"The":[2,254,592],"bone":[3],"marrow":[4],"microenvironment":[5],"modulates":[6],"response":[7,357],"of":[8,19,41,47,63,95,117,163,179,188,215,233,242,256,272,277,332,387,392,415,432,462,472,533,559,583,589],"acute":[9],"myeloid":[10],"leukemia":[11],"(AML)":[12],"to":[13,25,114,139,151,186,321,342,378,399,428,537,545,562,570,619,638],"therapy.":[14],"Thus":[15],"necessitating":[16],"the":[17,53,161,177,189,194,213,275,309,325,413,419,430,460,505,510,531,540,557,565],"identification":[18],"microenvironment-driven":[20],"signaling":[21,37,628],"mechanisms":[22],"that":[23,31,43,68,99,187,298,368,402,410,457],"contribute":[24],"AML":[26,32,157,205,278,283,335,394,450,463,535,560,584,612,630],"pathogenesis.":[27],"We":[28,147,175,211],"recently":[29,70,91],"showed":[30,98,297,340,397,409],"growth":[33,640],"depends":[34],"on":[35,171,261],"IL-1":[36,50,56,420],"in":[38,77,125,155,198,217,308,418,426,446,611,617,629],"a":[39,45,60,73,85,92,122,239,355,383,389,470,515,607],"majority":[40],"cases":[42],"include":[44],"spectrum":[46],"genetic":[48,144,209,473,614],"aberrations.":[49],"signals":[51],"through":[52],"serine/threonine":[54],"kinase":[55,58,292,311],"receptor-associated":[57],"(IRAK1),":[59],"central":[61],"mediator":[62],"immune":[64],"and":[65,127,193,202,225,228,246,266,281,287,290,305,314,328,337,424,443,466,481,501,509,586,598,622,631,641],"inflammatory":[66,434],"responses":[67],"was":[69],"suggested":[71],"as":[72,84,121],"potential":[74,490,608,646],"therapeutic":[75,123,609],"target":[76,610],"leukemia.":[78],"Pacritinib":[79,572],"is":[80,606],"currently":[81],"under":[82],"development":[83],"small-molecule":[86],"JAK2":[87,195,621],"inhibitor":[88,191,196,507,512],"for":[89,165,403],"myelofibrosis;":[90],"kinome":[93],"screen":[94],"429":[96],"kinases":[97],"pacritinib":[100,120,164,216,299,318,343,400,411,440,458,495,524,550],"also":[101,602],"inhibits":[102,412],"IRAK1":[103,118,153,273,310,423,486,597,605,627],"activity":[104,130,414,445],"(IC50":[105],"=":[106,346,350],"13.6":[107],"nM).":[108],"Here":[109],"we":[110,167,493],"provide":[111],"further":[112],"evidence":[113],"support":[115],"targeting":[116],"by":[119,285,484],"strategy":[124],"AML,":[126],"show":[128],"synergistic":[129],"with":[131,207,219,303,354,370,437,496,504,514,521,633],"histone":[132],"deacetylase":[133],"(HDAC)":[134],"or":[135,360,362,373,448,525,551,578,635],"bromodomain":[136],"(BET)":[137],"inhibitors":[138,580,637],"overcome":[140],"drug":[141,257],"resistance":[142,319],"across":[143,613],"subtypes.":[145,615],"Methods:":[146],"used":[148],"inducible":[149],"shRNA":[150],"reduce":[152],"levels":[154],"primary":[156,204,282,393,464,534],"cells.":[158],"To":[159,488],"validate":[160],"selectivity":[162],"IRAK1,":[166,323],"performed":[168],"targeted":[169],"mutagenesis":[170],"key":[172],"interacting":[173],"residues.":[174],"compared":[176,320],"efficacy":[178],"pacritinib,":[180],"an":[181],"established":[182],"dual":[183],"FLT3/JAK2":[184],"inhibitor,":[185],"FLT3":[190,442,623],"quizartinib":[192,374,404],"ruxolitinib":[197,371],"12":[199],"cell":[200,262,279,338,467,574],"lines":[201,280,339,468],"46":[203],"samples":[206,336,395,465],"various":[208,220,433],"lesions.":[210],"tested":[212,237],"synergy":[214,503],"combination":[218,247,491,516],"drugs,":[221],"including":[222,422,475],"HDAC,":[223],"BET,":[224],"BTK":[226],"inhibitors,":[227],"BH3":[229],"mimetic.":[230],"Equimolar":[231],"concentrations":[232],"both":[234],"agents":[235,497],"were":[236,249,259],"at":[238],"dose":[240],"gradient":[241],"1.0-5000":[243],"nM.":[244],"Synergy":[245],"index":[248,517],"calculated":[250],"using":[251],"Calcusyn":[252],"software.":[253],"effects":[255],"treatments":[258],"evaluated":[260],"viability,":[263],"survival,":[264],"differentiation,":[265,643],"downstream":[267,416],"signaling.":[268],"Results:":[269],"Genetic":[270],"knockdown":[271],"reduced":[274,288,459,530,543,556,568,587],"viability":[276,461,532,544,558,569],"cells":[284,536,561,585],"70%":[286],"p38":[289],"ERK1/2":[291],"activity.":[293,487],"Molecular":[294],"docking":[295],"simulation":[296],"forms":[300],"favorable":[301],"interactions":[302],"D298":[304],"S295":[306],"residues":[307],"domain.":[312],"IRAK1D298K":[313],"IRAK1S295D":[315],"conferred":[316],"significant":[317],"native":[322],"confirming":[324],"selective":[326],"binding":[327],"on-target":[329],"inhibitory":[330],"effect":[331],"pacritinib.":[333],"Primary":[334],"sensitivity":[341,398],"(median":[344],"IC50":[345,363],"90":[347],"nm,":[348],"range":[349],"2.0-1000":[351],"nM,":[352,382],"p<0.004),":[353],"higher":[356,390],"rate":[358],"(44/46":[359],"96%,":[361],"<":[364,380],"1000":[365,381],"nM)":[366],"than":[367,401],"observed":[369],"(15%)":[372],"(80%).":[375],"With":[376],"regard":[377],"IC90":[379],"more":[384],"stringent":[385],"measure":[386],"efficacy,":[388],"percentage":[391],"(33%)":[396],"(13%,":[405],"p<0.0001).":[406],"Mechanistic":[407],"studies":[408],"effectors":[417],"pathway,":[421],"p38,":[425],"addition":[427,618],"inhibiting":[429,485],"secretion":[431],"cytokines.":[435],"Consistent":[436],"previous":[438],"studies,":[439],"inhibited":[441],"JAK2/JAK3":[444],"FLT3-":[447],"JAK-dependent":[449],"cells,":[451],"respectively.":[452],"Additionally,":[453],"our":[454],"data":[455],"suggest":[456],"harboring":[469],"variety":[471],"abnormalities,":[474],"TET2,":[476],"MLL,":[477],"ASXL1,":[478],"NPM1,":[479],"CEBPA,":[480],"RAS":[482],"mutations,":[483],"identify":[489],"therapies,":[492],"combined":[494,541,566],"from":[498],"several":[499],"classes":[500],"found":[502],"HDAC":[506,577,634],"panobinostat":[508,554],"BET":[511,579,636],"JQ1":[513,528],"<1.":[518],"Specifically,":[519],"treatment":[520,542,567],"50":[522,526,548],"nM":[523,527,549,553],"alone":[529,555],"50%,":[538,563],"while":[539,564,576],"~25%.":[546],"Similarly,":[547],"20":[552],"~10%.":[571],"blocked":[573,594],"growth,":[575],"promoted":[581],"differentiation":[582],"numbers":[588],"early":[590],"progenitors.":[591],"combinations":[593],"not":[595],"only":[596],"ERK":[599],"activity,":[600],"but":[601],"c-Myc.":[603],"Conclusions:":[604],"Pacritinib,":[616],"suppressing":[620],"signaling,":[624],"specifically":[625],"blocks":[626],"synergizes":[632],"block":[639],"promote":[642],"establishing":[644],"its":[645],"clinical":[647],"utility.":[648],"Disclosures":[649],"Druker:":[650],"Agios:":[651],"Honoraria;":[652],"Ambit":[653],"BioSciences:":[654],"Consultancy;":[655,667,695],"ARIAD:":[656],"Patents":[657,663,685,712,723],"&":[658,664,686,713,724],"Royalties,":[659],"Research":[660,679,716,720,740],"Funding;":[661,680,717,721],"Array:":[662],"Royalties;":[665,687,714,725],"AstraZeneca:":[666],"Blueprint":[668],"Medicines:":[669],"Consultancy,":[670,689,698,705,709],"Equity":[671,682,690,706,710,732],"Ownership,":[672,711,733],"Other:":[673,699,734],"travel,":[674,700],"accommodations,":[675,701],"expenses":[676,702],";":[677,703],"BMS:":[678],"CTI:":[681],"Ownership;":[683,691,707],"Curis:":[684],"Cylene:":[688],"D3":[692],"Oncology":[693],"Solutions:":[694],"Gilead":[696],"Sciences:":[697],"Lorus:":[704],"MolecularMD:":[708],"Novartis:":[715],"Oncotide":[718],"Pharmaceuticals:":[719],"Pfizer:":[722],"Roche:":[726],"Consultancy.":[727],"Singer:CTI":[728],"BioPharma":[729,738],"Corp.:":[730],"Employment,":[731],"Leadership":[735],".":[736],"Agarwal:CTI":[737],"Corp:":[739],"Funding.":[741]},"counts_by_year":[{"year":2021,"cited_by_count":1},{"year":2020,"cited_by_count":1},{"year":2019,"cited_by_count":1}],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2019-10-18T00:00:00"}