Ontology type: schema:ScholarlyArticle Open Access: True
2019-12
AUTHORSHaijiao Zhang, Samantha Savage, Anna Reister Schultz, Daniel Bottomly, Libbey White, Erik Segerdell, Beth Wilmot, Shannon K. McWeeney, Christopher A. Eide, Tamilla Nechiporuk, Amy Carlos, Rachel Henson, Chenwei Lin, Robert Searles, Hoang Ho, Yee Ling Lam, Richard Sweat, Courtney Follit, Vinay Jain, Evan Lind, Gautam Borthakur, Guillermo Garcia-Manero, Farhad Ravandi, Hagop M. Kantarjian, Jorge Cortes, Robert Collins, Daelynn R. Buelow, Sharyn D. Baker, Brian J. Druker, Jeffrey W. Tyner
ABSTRACTFLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications and resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit in heavily pretreated relapsed/refractory AML patients, responses are transient and relapse eventually occurs. Here, to investigate the mechanisms of crenolanib resistance, we perform whole exome sequencing of AML patient samples before and after crenolanib treatment. Unlike other FLT3 inhibitors, crenolanib does not induce FLT3 secondary mutations, and mutations of the FLT3 gatekeeper residue are infrequent. Instead, mutations of NRAS and IDH2 arise, mostly as FLT3-independent subclones, while TET2 and IDH1 predominantly co-occur with FLT3-mutant clones and are enriched in crenolanib poor-responders. The remaining patients exhibit post-crenolanib expansion of mutations associated with epigenetic regulators, transcription factors, and cohesion factors, suggesting diverse genetic/epigenetic mechanisms of crenolanib resistance. Drug combinations in experimental models restore crenolanib sensitivity. More... »
PAGES244
http://scigraph.springernature.com/pub.10.1038/s41467-018-08263-x
DOIhttp://dx.doi.org/10.1038/s41467-018-08263-x
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1111348259
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/30651561
JSON-LD is the canonical representation for SciGraph data.
TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT
[
{
"@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json",
"about": [
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Oncology and Carcinogenesis",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Medical and Health Sciences",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Adult",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Aged",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Aged, 80 and over",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Animals",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Antineoplastic Combined Chemotherapy Protocols",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Benzimidazoles",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cell Line, Tumor",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Drug Resistance, Neoplasm",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Drug Screening Assays, Antitumor",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Epigenesis, Genetic",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Female",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "GTP Phosphohydrolases",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "HEK293 Cells",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Humans",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Inhibitory Concentration 50",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Isocitrate Dehydrogenase",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Leukemia, Myeloid, Acute",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Male",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Membrane Proteins",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Mice",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Middle Aged",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Mutation",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Piperidines",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Protein Kinase Inhibitors",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Pyridones",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Pyrimidinones",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Tandem Repeat Sequences",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Treatment Outcome",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Whole Exome Sequencing",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "fms-Like Tyrosine Kinase 3",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA",
"Division of Hematology and Medical Oncology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Zhang",
"givenName": "Haijiao",
"id": "sg:person.013502474053.06",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013502474053.06"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA",
"Division of Hematology and Medical Oncology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Savage",
"givenName": "Samantha",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA",
"Division of Hematology and Medical Oncology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Schultz",
"givenName": "Anna Reister",
"id": "sg:person.014300054453.21",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014300054453.21"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Bottomly",
"givenName": "Daniel",
"id": "sg:person.01357077705.33",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01357077705.33"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "White",
"givenName": "Libbey",
"id": "sg:person.015121036041.55",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015121036041.55"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Segerdell",
"givenName": "Erik",
"id": "sg:person.0674467030.41",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0674467030.41"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Wilmot",
"givenName": "Beth",
"id": "sg:person.01310200344.85",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01310200344.85"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "McWeeney",
"givenName": "Shannon K.",
"id": "sg:person.01300252534.27",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01300252534.27"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Howard Hughes Medical Institute",
"id": "https://www.grid.ac/institutes/grid.413575.1",
"name": [
"Division of Hematology and Medical Oncology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA",
"Howard Hughes Medical Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Eide",
"givenName": "Christopher A.",
"id": "sg:person.0617334452.44",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0617334452.44"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA",
"Division of Hematology and Medical Oncology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Nechiporuk",
"givenName": "Tamilla",
"id": "sg:person.0776517541.59",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0776517541.59"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Integrated Genomics, Knight Cancer Institute, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Carlos",
"givenName": "Amy",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Integrated Genomics, Knight Cancer Institute, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Henson",
"givenName": "Rachel",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Integrated Genomics, Knight Cancer Institute, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Lin",
"givenName": "Chenwei",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Integrated Genomics, Knight Cancer Institute, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Searles",
"givenName": "Robert",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Arog Pharmaceuticals (United States)",
"id": "https://www.grid.ac/institutes/grid.428101.e",
"name": [
"AROG Pharmaceuticals, 75240, Dallas, TX, USA"
],
"type": "Organization"
},
"familyName": "Ho",
"givenName": "Hoang",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Arog Pharmaceuticals (United States)",
"id": "https://www.grid.ac/institutes/grid.428101.e",
"name": [
"AROG Pharmaceuticals, 75240, Dallas, TX, USA"
],
"type": "Organization"
},
"familyName": "Lam",
"givenName": "Yee Ling",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Arog Pharmaceuticals (United States)",
"id": "https://www.grid.ac/institutes/grid.428101.e",
"name": [
"AROG Pharmaceuticals, 75240, Dallas, TX, USA"
],
"type": "Organization"
},
"familyName": "Sweat",
"givenName": "Richard",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Arog Pharmaceuticals (United States)",
"id": "https://www.grid.ac/institutes/grid.428101.e",
"name": [
"AROG Pharmaceuticals, 75240, Dallas, TX, USA"
],
"type": "Organization"
},
"familyName": "Follit",
"givenName": "Courtney",
"id": "sg:person.01057177072.90",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01057177072.90"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Arog Pharmaceuticals (United States)",
"id": "https://www.grid.ac/institutes/grid.428101.e",
"name": [
"AROG Pharmaceuticals, 75240, Dallas, TX, USA"
],
"type": "Organization"
},
"familyName": "Jain",
"givenName": "Vinay",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Molecular Microbiology & Immunology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Lind",
"givenName": "Evan",
"type": "Person"
},
{
"affiliation": {
"alternateName": "The University of Texas MD Anderson Cancer Center",
"id": "https://www.grid.ac/institutes/grid.240145.6",
"name": [
"The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA"
],
"type": "Organization"
},
"familyName": "Borthakur",
"givenName": "Gautam",
"id": "sg:person.012461014557.36",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012461014557.36"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "The University of Texas MD Anderson Cancer Center",
"id": "https://www.grid.ac/institutes/grid.240145.6",
"name": [
"The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA"
],
"type": "Organization"
},
"familyName": "Garcia-Manero",
"givenName": "Guillermo",
"id": "sg:person.0625002522.24",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0625002522.24"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "The University of Texas MD Anderson Cancer Center",
"id": "https://www.grid.ac/institutes/grid.240145.6",
"name": [
"The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA"
],
"type": "Organization"
},
"familyName": "Ravandi",
"givenName": "Farhad",
"id": "sg:person.01234653773.64",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01234653773.64"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "The University of Texas MD Anderson Cancer Center",
"id": "https://www.grid.ac/institutes/grid.240145.6",
"name": [
"The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA"
],
"type": "Organization"
},
"familyName": "Kantarjian",
"givenName": "Hagop M.",
"id": "sg:person.07607502677.73",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07607502677.73"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "The University of Texas MD Anderson Cancer Center",
"id": "https://www.grid.ac/institutes/grid.240145.6",
"name": [
"The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA"
],
"type": "Organization"
},
"familyName": "Cortes",
"givenName": "Jorge",
"type": "Person"
},
{
"affiliation": {
"alternateName": "The University of Texas Southwestern Medical Center",
"id": "https://www.grid.ac/institutes/grid.267313.2",
"name": [
"University of Texas Southwestern Medical Center, 75390, Dallas, TX, USA"
],
"type": "Organization"
},
"familyName": "Collins",
"givenName": "Robert",
"type": "Person"
},
{
"affiliation": {
"alternateName": "The Ohio State University",
"id": "https://www.grid.ac/institutes/grid.261331.4",
"name": [
"The Ohio State University College of Pharmacy and Comprehensive Cancer Center, 43210, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Buelow",
"givenName": "Daelynn R.",
"id": "sg:person.01220223031.46",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01220223031.46"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "The Ohio State University",
"id": "https://www.grid.ac/institutes/grid.261331.4",
"name": [
"The Ohio State University College of Pharmacy and Comprehensive Cancer Center, 43210, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Baker",
"givenName": "Sharyn D.",
"id": "sg:person.014334666047.33",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014334666047.33"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Howard Hughes Medical Institute",
"id": "https://www.grid.ac/institutes/grid.413575.1",
"name": [
"Division of Hematology and Medical Oncology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA",
"Howard Hughes Medical Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Druker",
"givenName": "Brian J.",
"id": "sg:person.012015172137.23",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012015172137.23"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Oregon Health & Science University",
"id": "https://www.grid.ac/institutes/grid.5288.7",
"name": [
"Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA",
"Division of Hematology and Medical Oncology, Oregon Health & Science University Knight Cancer Institute, 97239, Portland, OR, USA"
],
"type": "Organization"
},
"familyName": "Tyner",
"givenName": "Jeffrey W.",
"id": "sg:person.0617571351.54",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0617571351.54"
],
"type": "Person"
}
],
"citation": [
{
"id": "sg:pub.10.1038/nbt.2514",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1000477771",
"https://doi.org/10.1038/nbt.2514"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1200/jco.2011.36.9868",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1001929453"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.3109/10428194.2015.1132420",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1002272127"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nmeth.3047",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1003995336",
"https://doi.org/10.1038/nmeth.3047"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2011-02-334136",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1005297991"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2014-10-605808",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1005648199"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1073/pnas.1320661111",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1008934321"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s00277-016-2616-z",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1010663437",
"https://doi.org/10.1007/s00277-016-2616-z"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2007-05-091215",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1010761990"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/cncr.28705",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1011799651"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.ccell.2015.03.009",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1012040027"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/0008-5472.can-15-1015",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1012737808"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2005-06-2469",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1013576890"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1056/nejmoa1516192",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1016166624"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/prp2.149",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1018270796"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood.v98.6.1752",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1018630492"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2013-01-480228",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1018811414"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2006-05-023804",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1020754402"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.ccr.2007.11.005",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1021461434"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1177/2040620714532123",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1023811413"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1177/2040620714532123",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1023811413"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2016-01-693879",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1023980993"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1056/nejmoa1301689",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1025463655"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/leu.2013.14",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1026170547",
"https://doi.org/10.1038/leu.2013.14"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2014-04-531871",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1026486489"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2013-07-513044",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1027048980"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2002-05-1440",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1028925033"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.leu.2403099",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1029950764",
"https://doi.org/10.1038/sj.leu.2403099"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.leu.2403099",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1029950764",
"https://doi.org/10.1038/sj.leu.2403099"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1073/pnas.0709662105",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1030668301"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1101/gr.107524.110",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1032096953"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/leu.2016.293",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1033270843",
"https://doi.org/10.1038/leu.2016.293"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1056/nejmoa1408617",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1037067588"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1101/gr.129684.111",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1038753295"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/leu.2012.52",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1040537168",
"https://doi.org/10.1038/leu.2012.52"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature11016",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1041040113",
"https://doi.org/10.1038/nature11016"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2011-06-363960",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1041453315"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2013-10-529313",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1042650803"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/1078-0432.ccr-13-1323",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1045686740"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/leu.2015.165",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1045744906",
"https://doi.org/10.1038/leu.2015.165"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.leukres.2011.08.014",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1046533427"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1093/bioinformatics/btq330",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1047117020"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1371/journal.pone.0078398",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1048098592"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2015-05-646240",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1048375040"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/2159-8290.cd-15-0060",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1049231023"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2012-07-442871",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1051560452"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/0008-5472.can-15-3569",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1063216119"
],
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1079060078",
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1079265240",
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2016-04-711820",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1085464536"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2017-05-782292",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1085618912"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1056/nejmoa1614359",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1086135118"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1200/jco.2016.34.15_suppl.7008",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1106842457"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/s41586-018-0623-z",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1107663718",
"https://doi.org/10.1038/s41586-018-0623-z"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/s41586-018-0623-z",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1107663718",
"https://doi.org/10.1038/s41586-018-0623-z"
],
"type": "CreativeWork"
}
],
"datePublished": "2019-12",
"datePublishedReg": "2019-12-01",
"description": "FLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications and resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit in heavily pretreated relapsed/refractory AML patients, responses are transient and relapse eventually occurs. Here, to\u00a0investigate the mechanisms of crenolanib resistance, we perform whole exome sequencing of AML patient samples before and after crenolanib treatment. Unlike other FLT3 inhibitors, crenolanib does not induce FLT3 secondary mutations, and mutations of the FLT3 gatekeeper residue are infrequent. Instead, mutations of NRAS and IDH2 arise, mostly as FLT3-independent subclones, while TET2 and IDH1 predominantly co-occur with FLT3-mutant clones and are enriched in crenolanib poor-responders. The remaining patients exhibit post-crenolanib expansion of mutations associated with epigenetic regulators, transcription factors, and cohesion factors, suggesting diverse genetic/epigenetic mechanisms of crenolanib resistance. Drug combinations in experimental models restore crenolanib sensitivity.",
"genre": "research_article",
"id": "sg:pub.10.1038/s41467-018-08263-x",
"inLanguage": [
"en"
],
"isAccessibleForFree": true,
"isFundedItemOf": [
{
"id": "sg:grant.2438864",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.7025966",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2480359",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.7072602",
"type": "MonetaryGrant"
}
],
"isPartOf": [
{
"id": "sg:journal.1043282",
"issn": [
"2041-1723"
],
"name": "Nature Communications",
"type": "Periodical"
},
{
"issueNumber": "1",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "10"
}
],
"name": "Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanisms",
"pagination": "244",
"productId": [
{
"name": "readcube_id",
"type": "PropertyValue",
"value": [
"f75784579cbf769a52e7fdecce28444d6e064a4c7509f8b78e360871a76d679d"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"30651561"
]
},
{
"name": "nlm_unique_id",
"type": "PropertyValue",
"value": [
"101528555"
]
},
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1038/s41467-018-08263-x"
]
},
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1111348259"
]
}
],
"sameAs": [
"https://doi.org/10.1038/s41467-018-08263-x",
"https://app.dimensions.ai/details/publication/pub.1111348259"
],
"sdDataset": "articles",
"sdDatePublished": "2019-04-11T12:39",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000363_0000000363/records_70043_00000003.jsonl",
"type": "ScholarlyArticle",
"url": "https://www.nature.com/articles/s41467-018-08263-x"
}
]Download the RDF metadata as:Â json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41467-018-08263-x'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41467-018-08263-x'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41467-018-08263-x'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41467-018-08263-x'
This table displays all metadata directly associated to this object as RDF triples.
571 TRIPLES
21 PREDICATES
111 URIs
51 LITERALS
39 BLANK NODES