{"id":"https://openalex.org/W2334184770","doi":"https://doi.org/10.1182/blood.v122.21.479.479","title":"DNMT3A R882H Overexpression Leads To Hematopoietic and Skin Alterations In Transgenic Mice","display_name":"DNMT3A R882H Overexpression Leads To Hematopoietic and Skin Alterations In Transgenic Mice","publication_year":2013,"publication_date":"2013-11-15","ids":{"openalex":"https://openalex.org/W2334184770","doi":"https://doi.org/10.1182/blood.v122.21.479.479","mag":"2334184770"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v122.21.479.479","doi":"https://doi.org/10.1182/blood.v122.21.479.479","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v122.21.479.479","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/A5000366460","display_name":"Angela Maria Verdoni","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I204465549","display_name":"Washington University in St. Louis","ror":"https://ror.org/01yc7t268","country_code":"US","type":"education","lineage":["https://openalex.org/I204465549"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Angela M. Verdoni","raw_affiliation_strings":["Department of Medicine, Washington University School of Medicine, Siteman Cancer Center, St Louis, MO, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, Washington University School of Medicine, Siteman Cancer Center, St Louis, MO, USA,","institution_ids":["https://openalex.org/I204465549"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008195600","display_name":"Christopher B. Cole","orcid":"https://orcid.org/0000-0003-1033-9377","observed_orcids":["https://orcid.org/0000-0003-1033-9377"]},"institutions":[{"id":"https://openalex.org/I204465549","display_name":"Washington University in St. Louis","ror":"https://ror.org/01yc7t268","country_code":"US","type":"education","lineage":["https://openalex.org/I204465549"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Christopher B Cole","raw_affiliation_strings":["Department of Medicine, Washington University School of Medicine, Siteman Cancer Center, St Louis, MO, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, Washington University School of Medicine, Siteman Cancer Center, St Louis, MO, USA,","institution_ids":["https://openalex.org/I204465549"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5031896350","display_name":"Jeffery M. Klco","orcid":"https://orcid.org/0000-0003-2961-6960","observed_orcids":["https://orcid.org/0000-0003-2961-6960"]},"institutions":[{"id":"https://openalex.org/I204465549","display_name":"Washington University in St. Louis","ror":"https://ror.org/01yc7t268","country_code":"US","type":"education","lineage":["https://openalex.org/I204465549"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jeffery M. Klco","raw_affiliation_strings":["Department of Pathology and Immunology, Washington University, St. Louis, MO, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pathology and Immunology, Washington University, St. Louis, MO, USA,","institution_ids":["https://openalex.org/I204465549"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5076598094","display_name":"Timothy James Ley","orcid":"https://orcid.org/0000-0002-9913-0520","observed_orcids":["https://orcid.org/0000-0002-9913-0520"]},"institutions":[{"id":"https://openalex.org/I204465549","display_name":"Washington University in St. Louis","ror":"https://ror.org/01yc7t268","country_code":"US","type":"education","lineage":["https://openalex.org/I204465549"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Timothy J. Ley","raw_affiliation_strings":["Washington University School of Medicine, St. Louis, MO, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Washington University School of Medicine, St. Louis, MO, USA","institution_ids":["https://openalex.org/I204465549"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I204465549"],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":0.4329,"has_fulltext":false,"cited_by_count":4,"citation_normalized_percentile":{"value":0.6943553,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":96},"biblio":{"volume":"122","issue":"21","first_page":"479","last_page":"479"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.9955999851226807,"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":0.9955999851226807,"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/T10269","display_name":"Epigenetics and DNA Methylation","score":0.001500000013038516,"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/T11559","display_name":"Retinoids in leukemia and cellular processes","score":0.00039999998989515007,"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/dnmt3a","display_name":"DNMT3A","score":0.8820000290870667},{"id":"https://openalex.org/keywords/acute-myeloid-leukemia","display_name":"acute myeloid leukemia","score":0.8029999732971191},{"id":"https://openalex.org/keywords/myelodysplastic-syndrome","display_name":"myelodysplastic syndrome","score":0.9649999737739563},{"id":"https://openalex.org/keywords/hypomorphic-mutation","display_name":"hypomorphic mutation","score":0.4650000035762787},{"id":"https://openalex.org/keywords/dominant-negative-inhibition","display_name":"dominant negative inhibition","score":0.7739999890327454},{"id":"https://openalex.org/keywords/hematopoiesis","display_name":"hematopoiesis","score":0.7950000166893005},{"id":"https://openalex.org/keywords/hyperpigmentation","display_name":"hyperpigmentation","score":0.6019999980926514},{"id":"https://openalex.org/keywords/transgenic-mouse-model","display_name":"transgenic mouse model","score":0.6399999856948853},{"id":"https://openalex.org/keywords/tetracycline-inducible-gene-expression","display_name":"tetracycline-inducible expression","score":0.824999988079071},{"id":"https://openalex.org/keywords/bone-marrow","display_name":"bone marrow","score":0.4959999918937683},{"id":"https://openalex.org/keywords/epigenetic-regulation","display_name":"epigenetic regulation","score":0.36000001430511475},{"id":"https://openalex.org/keywords/dna-methylation","display_name":"DNA methylation","score":0.574999988079071}],"concepts":[{"id":"https://openalex.org/C102230213","wikidata":"https://www.wikidata.org/wiki/Q430117","display_name":"Transgene","level":3,"score":0.68740314245224},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.631589412689209},{"id":"https://openalex.org/C141035611","wikidata":"https://www.wikidata.org/wiki/Q5532934","display_name":"Genetically modified mouse","level":4,"score":0.616538405418396},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5890869498252869},{"id":"https://openalex.org/C109159458","wikidata":"https://www.wikidata.org/wiki/Q919283","display_name":"Haematopoiesis","level":3,"score":0.5727617144584656},{"id":"https://openalex.org/C2780007613","wikidata":"https://www.wikidata.org/wiki/Q546523","display_name":"Bone marrow","level":2,"score":0.565505862236023},{"id":"https://openalex.org/C2779703530","wikidata":"https://www.wikidata.org/wiki/Q837174","display_name":"Erythropoiesis","level":3,"score":0.4739515781402588},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.421514630317688},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.4195408821105957},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.28367578983306885},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.24815517663955688},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.20460590720176697},{"id":"https://openalex.org/C28328180","wikidata":"https://www.wikidata.org/wiki/Q48196","display_name":"Stem cell","level":2,"score":0.19823312759399414},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.13860806822776794},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.0886206328868866},{"id":"https://openalex.org/C2778248108","wikidata":"https://www.wikidata.org/wiki/Q5445","display_name":"Anemia","level":2,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v122.21.479.479","doi":"https://doi.org/10.1182/blood.v122.21.479.479","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v122.21.479.479","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":0.9391000270843506,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"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/W2589634897","https://openalex.org/W2536840886","https://openalex.org/W2597520619","https://openalex.org/W2344181275","https://openalex.org/W2979994420","https://openalex.org/W2522314764","https://openalex.org/W2993003377","https://openalex.org/W2934382244","https://openalex.org/W2592884968","https://openalex.org/W2979782950"],"abstract_inverted_index":{"Somatic":[0],"mutations":[1,32],"in":[2,11,23,33,58,144,155,173,224,232,242,263,266,275,381,400,417,455,558,605,611,632,642,657,678,707,710],"the":[3,52,106,112,115,119,129,138,145,153,156,165,174,179,188,245,255,373,382,397,401,432,456,474,511,550,553,627,633,691],"DNA":[4],"methyltransferase":[5],"gene,":[6],"DNMT3A,":[7,75],"have":[8,237,272,491],"been":[9,238,273,290],"identified":[10],">30%":[12],"of":[13,25,44,73,109,114,121,183,221,244,318,337,361,375,431,448,464,499,514,531,552,574,585,590,596,629,693,716],"de":[14],"novo":[15],"AML":[16,59],"cases":[17,60],"with":[18,27,214,281,292,437,439,587],"a":[19,39,62,68,93,100,217,228,368,542,582,588,594,679,686],"normal":[20],"karyotype,":[21],"and":[22,78,118,133,148,227,248,377,420,487,503,540,547,593,674],">10%":[24,428],"patients":[26],"MDS.":[28],"To":[29],"understand":[30],"whether":[31,702],"DNMT3A":[34,50,55,89,110,131,140,190,197,223,342,477,515,609,630,667],"alter":[35],"hematopoiesis,":[36],"we":[37],"generated":[38],"transgenic":[40,212,508],"mouse":[41,472],"model":[42],"capable":[43],"overexpressing":[45,607],"either":[46],"wild":[47],"type":[48],"human":[49,83,196,222],"or":[51,87,265,269,353],"most":[53],"common":[54],"mutation":[56],"found":[57,489],"(R882H,":[61],"hypomorphic":[63],"variant":[64],"that":[65,163,195,626,666],"acts":[66],"as":[67,404,522,524],"potent":[69],"dominant":[70,637,687],"negative":[71,638,688],"inhibitor":[72],"WT":[74,86,130,189,608],"D.":[76],"Germain":[77],"T.":[79],"Ley,":[80],"unpublished).":[81],"Full-length":[82],"cDNAs":[84],"encoding":[85],"R882H":[88,139,215,303,310,320,343,478,516,578,631,668],"were":[90,142,348],"cloned":[91],"into":[92,651],"mammalian":[94],"expression":[95,108,113],"vector":[96],"directly":[97],"downstream":[98],"from":[99,209,345,444,473,534,577,614],"tetracycline":[101],"responsive":[102],"element.":[103],"This":[104],"facilitates":[105],"inducible":[107],"upon":[111,572],"rtTA":[116,324],"coactivator":[117],"presence":[120,374],"Doxycycline":[122],"(Dox).":[123],"A":[124,285,470],"single":[125,471],"founder":[126,135],"line":[127,225,233,305,312,321,346,479,560],"for":[128,137,240,278],"allele":[132,141],"two":[134],"lines":[136,213],"established":[143,291],"C57Bl6/J":[146],"background":[147],"subsequently":[149],"shown":[150],"to":[151,161,365,393,490,649,659,718],"express":[152],"transgene":[154],"bone":[157,181,207,402],"marrow":[158,182,208,267,403],"when":[159],"crossed":[160],"mice":[162,186,241,276,294,325,344,435,450,509,536,565,606,613],"carry":[164],"Rosa26-rtTA":[166],"allele,":[167],"which":[168],"is":[169,556],"expressed":[170,199,216],"ubiquitously":[171],"(including":[172],"skin,":[175],"see":[176],"below).":[177],"In":[178],"unfractionated":[180],"Dox":[184,210,252,283,296,332,338,528,619],"treated":[185,211,277],"carrying":[187],"transgene,":[191],"western":[192],"blots":[193],"revealed":[194],"was":[198,488,569,603],"3.5":[200],"fold":[201,219,230],"higher":[202],"than":[203],"endogenous":[204,694],"murine":[205],"DNMT3A;":[206],"4.5":[218],"excess":[220,231],"1,":[226],"16":[229],"2.":[234],"No":[235,260,600,713],"phenotypes":[236,704],"observed":[239,274],"any":[243,612,615],"8":[246,329],"experimental":[247],"control":[249,418],"genotypes":[250],"without":[251],"chow":[253,297],"(since":[254],"transgenes":[256],"are":[257,656,705],"not":[258,617],"expressed).":[259],"consistent":[261],"abnormalities":[262],"CBCs":[264],"morphology":[268],"progenitor":[270],"numbers":[271],"4-8":[279],"weeks":[280,330,526],"1%":[282],"chow.":[284,333,529],"tumor":[286],"watch":[287],"has":[288],"therefore":[289],"all":[293],"on":[295,331,527,618,640,690],"(WT":[298],"Tg":[299,304,311],"x":[300,307,314,323],"rtTA,":[301,308,315],"n=24;":[302],"1":[306,580],"n=20;":[309],"2":[313,322,347],"n=36).":[316],"One":[317],"36":[319],"became":[326,482],"moribund":[327,434,483],"at":[328,484,561],"After":[334],"6":[335],"months":[336,486,563,592],"chow,":[339],"13/36":[340],"(36.1%)":[341],"sacrificed":[349],"after":[350],"becoming":[351],"moribund,":[352],"died":[354],"before":[355],"analysis":[356],"could":[357],"be":[358],"performed.":[359],"Four":[360,430],"seven":[362],"analyzed":[363],"prior":[364],"death":[366],"demonstrated":[367],"leukocytosis":[369],"(WBC":[370],"range":[371,391,410],"30.8-40.32),":[372],"blast-like":[376],"immature":[378],"myeloid":[379,398,501],"cells":[380,425,677],"peripheral":[383],"blood":[384],"(2/7":[385,426],"mice),":[386,419],"mild":[387,543],"splenomegaly":[388,495],"(3/7":[389],"mice,":[390,409,427],"0.2g":[392],"0.25g),":[394],"shifts":[395],"toward":[396],"lineage":[399],"assessed":[405],"by":[406,423,684],"CD11b+":[407,424],"(4/7":[408],"69.0-84.3%":[411],"versus":[412],"53.24%":[413],"+/-":[414],"8.69%":[415],"SD":[416],"splenic":[421,497],"infiltration":[422,498],"composition).":[429],"7":[433,449],"presented":[436],"anemia,":[438],"hemoglobin":[440],"(Hgb)":[441],"levels":[442],"ranging":[443],"3.2-10.4":[445],"g/dl.":[446],"Six":[447],"had":[451],"erythroid":[452],"maturation":[453],"defects":[454],"marrow,":[457],"where":[458],"3/7":[459],"specifically":[460],"displayed":[461],"an":[462],"accumulation":[463],"proerythroblasts":[465],"(CD71":[466],"high/":[467],"Ter119":[468],"low).":[469],"lower":[475],"expressing":[476,510],"(line":[480,517],"1)":[481],"9":[485],"severe":[492],"anemia":[493],"(Hgb=3.6),":[494],"(0.7g),":[496],"mature":[500],"cells,":[502,645],"altered":[504],"erythropoiesis.":[505],"Some":[506],"doubly":[507],"high":[512],"level":[513],"2)":[518],"developed":[519,581],"extensive":[520],"alopecia":[521,568],"early":[523],"3":[525,562,591],"Examination":[530],"skin":[532,554,601,634,643,675],"sections":[533],"these":[535,623,703],"showed":[537],"epidermal":[538],"hyperplasia":[539],"acanthosis,":[541],"mixed":[544],"inflammatory":[545],"infiltrate,":[546],"follicular":[548],"plugging;":[549],"penetrance":[551,595],"phenotype":[555,602],"\u223c60%":[557],"this":[559,661],"(21/36":[564],"affected).":[566,599],"The":[567],"completely":[570],"reversible":[571],"withdrawal":[573],"Dox.":[575],"Mice":[576],"Line":[579],"milder":[583],"form":[584],"alopecia,":[586],"latency":[589],"60%":[597],"(12/20":[598],"apparent":[604],"(or":[610],"genotype":[616],"chow).":[620],"Taken":[621],"together,":[622],"data":[624,664],"suggest":[625,665],"overexpression":[628,669],"may":[635,670],"cause":[636],"effects":[639],"Dnmt3a":[641],"stem/progenitor":[644,676],"affecting":[646],"their":[647],"ability":[648],"differentiate":[650],"hair":[652],"follicles.":[653],"Further":[654],"experiments":[655],"progress":[658],"confirm":[660],"hypothesis.":[662],"Our":[663],"affect":[671],"both":[672,708],"hematopoietic":[673],"dose":[680],"dependent":[681],"manner,":[682],"perhaps":[683],"exerting":[685],"effect":[689],"function":[692],"Dnmt3a.":[695],"Experiments":[696],"currently":[697],"being":[698],"performed":[699],"will":[700],"determine":[701],"cell-autonomous":[706],"compartments":[709],"vivo.":[711],"Disclosures:":[712],"relevant":[714],"conflicts":[715],"interest":[717],"declare.":[719]},"counts_by_year":[{"year":2020,"cited_by_count":1},{"year":2019,"cited_by_count":1},{"year":2014,"cited_by_count":2}],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2016-06-24T00:00:00"}
