{"id":"https://openalex.org/W2337624766","doi":"https://doi.org/10.1182/blood.v122.21.4434.4434","title":"Intracellular Accumulation Of Light Chains Caused By Lenalidomide, and Mediated Via CRBN, Causes Major ER Stress and Is Implicated In The Synergistic Combination Of Imids and Proteasome Inhibitors","display_name":"Intracellular Accumulation Of Light Chains Caused By Lenalidomide, and Mediated Via CRBN, Causes Major ER Stress and Is Implicated In The Synergistic Combination Of Imids and Proteasome Inhibitors","publication_year":2013,"publication_date":"2013-11-15","ids":{"openalex":"https://openalex.org/W2337624766","doi":"https://doi.org/10.1182/blood.v122.21.4434.4434","mag":"2337624766"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v122.21.4434.4434","doi":"https://doi.org/10.1182/blood.v122.21.4434.4434","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v122.21.4434.4434","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","is_traditional":true,"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/A5025632074","display_name":"Sinto Sebastian","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210125099","display_name":"Mayo Clinic in Arizona","ror":"https://ror.org/03jp40720","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1330342723","https://openalex.org/I4210125099"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sinto Sebastian","raw_affiliation_strings":["Research, Mayo Clinic, Scottsdale, AZ, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Research, Mayo Clinic, Scottsdale, AZ, USA,","institution_ids":["https://openalex.org/I4210125099"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101766525","display_name":"Yuan Xiao Zhu","orcid":"https://orcid.org/0000-0003-0779-7756","observed_orcids":["https://orcid.org/0000-0003-0779-7756"]},"institutions":[{"id":"https://openalex.org/I4210125099","display_name":"Mayo Clinic in Arizona","ror":"https://ror.org/03jp40720","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1330342723","https://openalex.org/I4210125099"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Yuan Xiao Zhu","raw_affiliation_strings":["Research, Mayo Clinic, Scottsdale, AZ, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Research, Mayo Clinic, Scottsdale, AZ, USA,","institution_ids":["https://openalex.org/I4210125099"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5082845313","display_name":"Esteban Braggio","orcid":"https://orcid.org/0000-0003-3860-4830","observed_orcids":["https://orcid.org/0000-0003-3860-4830"]},"institutions":[{"id":"https://openalex.org/I4210125099","display_name":"Mayo Clinic in Arizona","ror":"https://ror.org/03jp40720","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1330342723","https://openalex.org/I4210125099"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Esteban Braggio","raw_affiliation_strings":["Division of Hematology - Oncology, Mayo Clinic, Scottsdale, AZ, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology - Oncology, Mayo Clinic, Scottsdale, AZ, USA,","institution_ids":["https://openalex.org/I4210125099"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085487269","display_name":"Sonali C. Panchabhai","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210125099","display_name":"Mayo Clinic in Arizona","ror":"https://ror.org/03jp40720","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1330342723","https://openalex.org/I4210125099"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sonali Panchabhai","raw_affiliation_strings":["Research, Mayo Clinic Airzona, Scottsdale, AZ, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Research, Mayo Clinic Airzona, Scottsdale, AZ, USA,","institution_ids":["https://openalex.org/I4210125099"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5109602566","display_name":"Chang\u2010Xin Shi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210125099","display_name":"Mayo Clinic in Arizona","ror":"https://ror.org/03jp40720","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1330342723","https://openalex.org/I4210125099"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Chang-Xin Shi","raw_affiliation_strings":["1Research, Mayo Clinic in Arizona,, Mayo Clinic in Arizona, Scottsdale, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Research, Mayo Clinic in Arizona,, Mayo Clinic in Arizona, Scottsdale, USA,","institution_ids":["https://openalex.org/I4210125099"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5087235686","display_name":"Gregory J. Ahmann","orcid":"https://orcid.org/0009-0005-1841-6017","observed_orcids":["https://orcid.org/0009-0005-1841-6017"]},"institutions":[{"id":"https://openalex.org/I4210125099","display_name":"Mayo Clinic in Arizona","ror":"https://ror.org/03jp40720","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1330342723","https://openalex.org/I4210125099"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Gregory Ahmann","raw_affiliation_strings":["Mayo Clinic Arizona, Scottsdale, AZ, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Mayo Clinic Arizona, Scottsdale, AZ, USA,","institution_ids":["https://openalex.org/I4210125099"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5004436275","display_name":"Peter Leif Bergsagel","orcid":"https://orcid.org/0000-0003-1523-7388","observed_orcids":["https://orcid.org/0000-0003-1523-7388"]},"institutions":[{"id":"https://openalex.org/I4210125099","display_name":"Mayo Clinic in Arizona","ror":"https://ror.org/03jp40720","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1330342723","https://openalex.org/I4210125099"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Leif Bergsagel","raw_affiliation_strings":["Hematological Malignancies, Mayo Clinic Scottsdale, Scottsdale, AZ, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Hematological Malignancies, Mayo Clinic Scottsdale, Scottsdale, AZ, USA,","institution_ids":["https://openalex.org/I4210125099"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5003015868","display_name":"Rafa\u00ebl Fonseca","orcid":"https://orcid.org/0000-0002-5938-3769","observed_orcids":["https://orcid.org/0000-0002-5938-3769"]},"institutions":[{"id":"https://openalex.org/I4210125099","display_name":"Mayo Clinic in Arizona","ror":"https://ror.org/03jp40720","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1330342723","https://openalex.org/I4210125099"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Rafael Fonseca","raw_affiliation_strings":["Division of Hematology and Oncology, Mayo Clinic in Arizona, Scottsdale, AZ, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology and Oncology, Mayo Clinic in Arizona, Scottsdale, AZ, USA","institution_ids":["https://openalex.org/I4210125099"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I4210125099"],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.26225536,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"122","issue":"21","first_page":"4434","last_page":"4434"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10649","display_name":"Multiple Myeloma Research and Treatments","score":0.989300012588501,"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/T10649","display_name":"Multiple Myeloma Research and Treatments","score":0.989300012588501,"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/T12534","display_name":"Protein Degradation and Inhibitors","score":0.006300000008195639,"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/T11150","display_name":"Endoplasmic Reticulum Stress and Disease","score":0.0007999999797903001,"subfield":{"id":"https://openalex.org/subfields/1307","display_name":"Cell 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/lenalidomide","display_name":"lenalidomide","score":0.9990000128746033},{"id":"https://openalex.org/keywords/multiple-myeloma","display_name":"multiple myeloma","score":0.8169999718666077},{"id":"https://openalex.org/keywords/cereblon","display_name":"cereblon","score":0.7559999823570251},{"id":"https://openalex.org/keywords/immunoglobulin-light-chains","display_name":"immunoglobulin light chains","score":0.8629999756813049},{"id":"https://openalex.org/keywords/endoplasmic-reticulum-stress","display_name":"endoplasmic reticulum stress","score":0.9869999885559082},{"id":"https://openalex.org/keywords/imidazole","display_name":"imidazole","score":0.5450000166893005},{"id":"https://openalex.org/keywords/proteasome-inhibitors","display_name":"proteasome inhibitors","score":0.9300000071525574},{"id":"https://openalex.org/keywords/bortezomib","display_name":"bortezomib","score":0.9710000157356262},{"id":"https://openalex.org/keywords/lenalidomide-resistance","display_name":"lenalidomide resistance","score":0.8190000057220459},{"id":"https://openalex.org/keywords/irf4","display_name":"IRF4","score":0.8220000267028809},{"id":"https://openalex.org/keywords/p53-degradation","display_name":"p53 degradation","score":0.7990000247955322},{"id":"https://openalex.org/keywords/xbp1","display_name":"XBP1","score":0.7839999794960022},{"id":"https://openalex.org/keywords/grp78","display_name":"GRP78","score":0.9409999847412109},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.6779999732971191},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.38600000739097595}],"concepts":[{"id":"https://openalex.org/C2778540781","wikidata":"https://www.wikidata.org/wiki/Q21112029","display_name":"Cereblon","level":5,"score":0.7512746453285217},{"id":"https://openalex.org/C2777478702","wikidata":"https://www.wikidata.org/wiki/Q419319","display_name":"Bortezomib","level":3,"score":0.7058279514312744},{"id":"https://openalex.org/C2776063141","wikidata":"https://www.wikidata.org/wiki/Q425681","display_name":"Lenalidomide","level":3,"score":0.6803379058837891},{"id":"https://openalex.org/C2776415932","wikidata":"https://www.wikidata.org/wiki/Q48743","display_name":"Western blot","level":3,"score":0.5719087719917297},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5411697030067444},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.5165364146232605},{"id":"https://openalex.org/C173396325","wikidata":"https://www.wikidata.org/wiki/Q1501275","display_name":"Gene knockdown","level":3,"score":0.49934864044189453},{"id":"https://openalex.org/C2778524551","wikidata":"https://www.wikidata.org/wiki/Q7227206","display_name":"Pomalidomide","level":4,"score":0.4743020832538605},{"id":"https://openalex.org/C27740335","wikidata":"https://www.wikidata.org/wiki/Q14878333","display_name":"Proteasome","level":2,"score":0.42950743436813354},{"id":"https://openalex.org/C2776364478","wikidata":"https://www.wikidata.org/wiki/Q467635","display_name":"Multiple myeloma","level":2,"score":0.37101423740386963},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.3661695420742035},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3506695628166199},{"id":"https://openalex.org/C134459356","wikidata":"https://www.wikidata.org/wiki/Q4274835","display_name":"Ubiquitin ligase","level":4,"score":0.21258637309074402},{"id":"https://openalex.org/C25602115","wikidata":"https://www.wikidata.org/wiki/Q407111","display_name":"Ubiquitin","level":3,"score":0.1714065670967102},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.16824471950531006},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.16412711143493652},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.09190189838409424},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v122.21.4434.4434","doi":"https://doi.org/10.1182/blood.v122.21.4434.4434","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v122.21.4434.4434","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":[{"score":0.9537000060081482,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"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/W1937746418","https://openalex.org/W4230137669","https://openalex.org/W2973147210","https://openalex.org/W2979972909","https://openalex.org/W2584338393","https://openalex.org/W2588370718","https://openalex.org/W2980152621","https://openalex.org/W4405041744","https://openalex.org/W947311794","https://openalex.org/W2922215828"],"abstract_inverted_index":{"Background":[0],"The":[1],"precise":[2],"molecular":[3],"mechanism":[4,284],"and":[5,62,87,91,100,118,129,182,186,199,203,236,310,322,327,349,362,402,438,451,489,520],"targets":[6],"of":[7,27,55,74,113,151,160,165,171,208,213,250,275,370,391,477,496,518,535,576,582,586,592,596,602],"lenalidomide":[8,75,103,114,143,251,268,304,330,343,364,400,416,437,447,474,519],"specific":[9],"anti-Multiple":[10],"Myeloma":[11],"(MM)":[12],"activity":[13,28,488],"remain":[14],"largely":[15],"unknown,":[16],"although,":[17],"cereblon":[18],"(CRBN)":[19],"has":[20,292],"been":[21,293],"identified":[22],"as":[23,32,177,374,501],"a":[24,33,163,283],"central":[25],"mediator":[26],"with":[29,70,111,121,205,436,441,446,455],"IRF-4":[30,50],"acting":[31],"downstream":[34],"molecule.":[35],"Lenalidomide":[36],"resistance":[37,401],"in":[38,157,162,175,184,220,225,242,255,270,306,333,357,384,395,399,426,486],"MM":[39,166,359,386,429,443,505,577,587,597],"cells":[40,108,194,222,246,287,397,444,506],"which,":[41],"despite":[42],"CRBN":[43,128,161,198,226,243,256,271,307,339,356],"depletion,":[44],"are":[45],"able":[46],"to":[47,72,78,125,288,290,344,461,507,525],"restore":[48],"their":[49],"levels":[51],"suggests":[52],"the":[53,158,276,368,494,515,526,533,583,593,603],"existence":[54],"alternative":[56],"pathways.":[57],"Methods":[58],"To":[59,366],"measure":[60],"apoptosis":[61,425,464],"gene":[63],"expression":[64,93],"analysis":[65],"1x":[66],"106cells":[67],"were":[68,83,94,109,134],"incubated":[69,110],"10\u03bcm":[71,112],"50\u03bcm":[73],"for":[76,115,123,197,342,448],"24":[77,124],"96":[79],"hours":[80,117,249],"before":[81],"they":[82],"examined":[84],"by":[85,96,136,179,280,286,354,542],"annexin-PI":[86],"FACS":[88],"analysis.":[89],"Gene":[90],"protein":[92,300,347,528],"measured":[95],"RT-PCR,":[97],"western":[98,180],"blot,":[99],"immunohistochemistry.":[101],"For":[102],"followed":[104,541],"bortezomib":[105,122,423,456,462,502,543],"serial":[106,536],"studies,":[107],"48":[116,126],"later":[119],"treated":[120,204,440,454,467],"hrs.":[127],"immunoglobulin":[130,153,346,380,478],"light":[131,371,381,393,479],"chain":[132,372,382,394],"knock-down":[133,257],"performed":[135],"lentiviral":[137],"mediated":[138,408,417],"shRNA.":[139],"Results":[140],"We":[141,190,295,313,431],"found":[142,233,297,328],"induces":[144,331],"Endoplasmic":[145],"reticulum":[146,406,509],"stress":[147,407],"(ERS)":[148],"via":[149],"accumulation":[150,170,348,373,476],"intracellular":[152,172],"proteins,":[154,241],"but":[155,223,253,335],"only":[156],"presence":[159,495],"panel":[164],"cell":[167,188,318,360,387,434],"lines.":[168,189],"This":[169,530],"proteins":[173],"resulted":[174,398],"ERS":[176,216,239,260,291,332,350,419],"documented":[178],"blot":[181,231],"RT-PCR":[183],"OPM2":[185,193,309,396],"MMIS":[187,311],"next":[191],"utilized":[192,285],"knocked":[195,378],"down":[196,301,379],"control,":[200],"non-target":[201],"(NT),":[202],"different":[206],"doses":[207],"lenalidomide.":[209],"After":[210],"three":[211],"days":[212,450],"treatment":[214,269,305,540],"an":[215,427],"response":[217],"was":[218,263,351],"occurring":[219],"OPM2-NT":[221],"not":[224,254,336],"knockdown":[227],"cells.":[228,258,273,312,338,468],"Using":[229],"Western":[230],"we":[232,377,471],"decreased":[234],"XBP-1u":[235],"increased":[237,459],"XBP-1s,":[238],"marker":[240,261],"positive":[244,272,308],"(NT)":[245],"after":[247,267,303,453],"72":[248],"treatment,":[252],"Another":[259],"GRP78/BiP":[262],"also":[264,296,503],"clearly":[265,457],"accumulated":[266],"Inactivation":[274],"tumor":[277],"suppressor":[278],"p53":[279,299],"degradation":[281],"is":[282,340],"adapt":[289],"reported.":[294],"that":[298,329,415,473,490],"regulated":[302],"have":[314],"analyzed":[315],"other":[316],"isogenic":[317,323],"lines":[319,435],"MM1.S":[320,334],"(lenalidomide-sensitive)":[321],"MM1.Sres":[324,337],"(lenalidomide-resistant)":[325],"HMCLs":[326],"important":[341],"induce":[345],"further":[352],"proved":[353],"over-expressing":[355],"OCI-My5":[358],"line":[361,388],"subsequent":[363],"treatment.":[365,546],"test":[367],"effect":[369,491,517],"ER":[375,483],"stressors,":[376],"lambda":[383,392],"human":[385],"OPM2.":[389],"Knock-down":[390],"it":[403],"induced":[404,424,463],"endoplasmic":[405,508],"anti-myeloma":[409,487],"activity.":[410],"Our":[411,512],"preliminary":[412],"data":[413,513,531],"reveals":[414],"progressive":[418,482],"can":[420],"positively":[421],"enhance":[422],"in-vitro":[428],"model.":[430],"pre-treated":[432,445],"myeloma":[433],"subsequently":[439],"bortezomib.":[442],"two":[449],"there":[452],"shown":[458],"sensitivity":[460],"than":[465],"non-pre-lenalidomide":[466],"Conclusion":[469],"Here":[470],"show":[472],"causes":[475],"chains,":[480],"inducing":[481],"stress,":[484],"resulting":[485],"depends":[492],"on":[493,579,589,599],"CRBN.":[497],"Proteasome":[498],"inhibitors":[499],"such":[500],"sensitize":[504],"stress-mediated":[510],"apoptosis.":[511],"demonstrated":[514],"synergistic":[516],"proteasome":[521],"inhibitors,":[522],"likely":[523],"due":[524],"augmented":[527],"stress.":[529],"support":[532],"use":[534],"therapy":[537],"utilizing":[538],"pre-lenalidomide":[539],"or":[544],"carfilzomib":[545],"Disclosures:":[547],"Fonseca:":[548],"Medtronic:":[549],"Consultancy;":[550,552,554,556,558,560,567,569,571],"Otsuka:":[551],"Celgene:":[553],"Genzyme:":[555],"BMS:":[557],"Lilly:":[559],"Onyx:":[561],"Consultancy,":[562],"Research":[563,573],"Funding;":[564,574],"Binding":[565],"Site:":[566],"Millennium:":[568],"AMGEN:":[570],"Cylene:":[572],"Prognostication":[575,585,595],"based":[578,588,598],"genetic":[580,590,600],"categorization":[581,591,601],"disease:":[584],"disease,":[594],"disease":[604],"Patents":[605],"&":[606],"Royalties.":[607]},"counts_by_year":[],"updated_date":"2026-10-14T16:39:01.820549","created_date":"2016-06-24T00:00:00"}
