PubMed:24895125 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/24895125","sourcedb":"PubMed","sourceid":"24895125","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/24895125","text":"Loss of TBL1XR1 disrupts glucocorticoid receptor recruitment to chromatin and results in glucocorticoid resistance in a B-lymphoblastic leukemia model.\nAlthough great advances have been made in the treatment of pediatric acute lymphoblastic leukemia, up to one of five patients will relapse, and their prognosis thereafter is dismal. We have previously identified recurrent deletions in TBL1XR1, which encodes for an F-box like protein responsible for regulating the nuclear hormone repressor complex stability. Here we model TBL1XR1 deletions in B-precursor ALL cell lines and show that TBL1XR1 knockdown results in reduced glucocorticoid receptor recruitment to glucocorticoid responsive genes and ultimately decreased glucocorticoid signaling caused by increased levels of nuclear hormone repressor 1 and HDAC3. Reduction in glucocorticoid signaling in TBL1XR1-depleted lines resulted in resistance to glucocorticoid agonists, but not to other chemotherapeutic agents. Importantly, we show that treatment with the HDAC inhibitor SAHA restores sensitivity to prednisolone in TBL1XR1-depleted cells. Altogether, our data indicate that loss of TBL1XR1 is a novel driver of glucocorticoid resistance in ALL and that epigenetic therapy may have future application in restoring drug sensitivity at relapse.","tracks":[{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":221,"end":249},"obj":"HP_0006721"},{"id":"T2","span":{"begin":241,"end":249},"obj":"HP_0001909"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":8,"end":15},"obj":"gene:79718"},{"id":"T1","span":{"begin":122,"end":144},"obj":"disease:C0023449"},{"id":"T2","span":{"begin":25,"end":48},"obj":"gene:2908"},{"id":"T3","span":{"begin":122,"end":144},"obj":"disease:C1961102"},{"id":"T4","span":{"begin":25,"end":48},"obj":"gene:2908"},{"id":"T5","span":{"begin":122,"end":144},"obj":"disease:C0023449"},{"id":"T6","span":{"begin":25,"end":48},"obj":"gene:2908"},{"id":"T7","span":{"begin":122,"end":144},"obj":"disease:C0023448"},{"id":"T8","span":{"begin":8,"end":15},"obj":"gene:79718"},{"id":"T9","span":{"begin":89,"end":114},"obj":"disease:C1841972"},{"id":"T10","span":{"begin":8,"end":15},"obj":"gene:79718"},{"id":"T11","span":{"begin":122,"end":144},"obj":"disease:C0023448"},{"id":"T12","span":{"begin":25,"end":48},"obj":"gene:2908"},{"id":"T13","span":{"begin":89,"end":114},"obj":"disease:C1841972"},{"id":"T14","span":{"begin":8,"end":15},"obj":"gene:79718"},{"id":"T15","span":{"begin":122,"end":144},"obj":"disease:C1961102"},{"id":"T16","span":{"begin":526,"end":533},"obj":"gene:79718"},{"id":"T17","span":{"begin":547,"end":562},"obj":"disease:C1292769"},{"id":"T18","span":{"begin":808,"end":813},"obj":"gene:8841"},{"id":"T19","span":{"begin":547,"end":562},"obj":"disease:C1292769"},{"id":"T20","span":{"begin":625,"end":648},"obj":"gene:2908"},{"id":"T21","span":{"begin":547,"end":562},"obj":"disease:C1292769"},{"id":"T22","span":{"begin":588,"end":595},"obj":"gene:79718"},{"id":"T23","span":{"begin":547,"end":562},"obj":"disease:C1292769"},{"id":"T24","span":{"begin":1144,"end":1151},"obj":"gene:79718"},{"id":"T25","span":{"begin":1173,"end":1198},"obj":"disease:C1841972"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"},{"id":"R5","pred":"associated_with","subj":"T8","obj":"T9"},{"id":"R6","pred":"associated_with","subj":"T10","obj":"T11"},{"id":"R7","pred":"associated_with","subj":"T12","obj":"T13"},{"id":"R8","pred":"associated_with","subj":"T14","obj":"T15"},{"id":"R9","pred":"associated_with","subj":"T16","obj":"T17"},{"id":"R10","pred":"associated_with","subj":"T18","obj":"T19"},{"id":"R11","pred":"associated_with","subj":"T20","obj":"T21"},{"id":"R12","pred":"associated_with","subj":"T22","obj":"T23"},{"id":"R13","pred":"associated_with","subj":"T24","obj":"T25"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"},{"subj":"T4","pred":"source","obj":"DisGeNET"},{"subj":"T5","pred":"source","obj":"DisGeNET"},{"subj":"T6","pred":"source","obj":"DisGeNET"},{"subj":"T7","pred":"source","obj":"DisGeNET"},{"subj":"T8","pred":"source","obj":"DisGeNET"},{"subj":"T9","pred":"source","obj":"DisGeNET"},{"subj":"T10","pred":"source","obj":"DisGeNET"},{"subj":"T11","pred":"source","obj":"DisGeNET"},{"subj":"T12","pred":"source","obj":"DisGeNET"},{"subj":"T13","pred":"source","obj":"DisGeNET"},{"subj":"T14","pred":"source","obj":"DisGeNET"},{"subj":"T15","pred":"source","obj":"DisGeNET"},{"subj":"T16","pred":"source","obj":"DisGeNET"},{"subj":"T17","pred":"source","obj":"DisGeNET"},{"subj":"T18","pred":"source","obj":"DisGeNET"},{"subj":"T19","pred":"source","obj":"DisGeNET"},{"subj":"T20","pred":"source","obj":"DisGeNET"},{"subj":"T21","pred":"source","obj":"DisGeNET"},{"subj":"T22","pred":"source","obj":"DisGeNET"},{"subj":"T23","pred":"source","obj":"DisGeNET"},{"subj":"T24","pred":"source","obj":"DisGeNET"},{"subj":"T25","pred":"source","obj":"DisGeNET"}]},{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":151},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":152,"end":333},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":334,"end":511},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":512,"end":814},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":815,"end":971},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":972,"end":1100},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":1101,"end":1303},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":151},"obj":"Sentence"},{"id":"T2","span":{"begin":152,"end":333},"obj":"Sentence"},{"id":"T3","span":{"begin":334,"end":511},"obj":"Sentence"},{"id":"T4","span":{"begin":512,"end":814},"obj":"Sentence"},{"id":"T5","span":{"begin":815,"end":971},"obj":"Sentence"},{"id":"T6","span":{"begin":972,"end":1100},"obj":"Sentence"},{"id":"T7","span":{"begin":1101,"end":1303},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"TextSentencer_T1","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T2","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T3","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T4","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T5","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T6","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T7","pred":"source","obj":"sentences"},{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"}]},{"project":"DisGeNet-2017-sample","denotations":[{"id":"T105","span":{"begin":8,"end":15},"obj":"gene:79718"},{"id":"T106","span":{"begin":122,"end":144},"obj":"disease:C0023448"},{"id":"T107","span":{"begin":25,"end":48},"obj":"gene:2908"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T105","obj":"T106"},{"id":"R2","pred":"associated_with","subj":"T105","obj":"T106"},{"id":"R3","pred":"associated_with","subj":"T105","obj":"T106"},{"id":"R4","pred":"associated_with","subj":"T107","obj":"T106"},{"id":"R5","pred":"associated_with","subj":"T107","obj":"T106"},{"id":"R6","pred":"associated_with","subj":"T107","obj":"T106"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T105","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T106","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T107","pred":"source","obj":"DisGeNet-2017-sample"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"24895125-0#8#15#gene79718","span":{"begin":8,"end":15},"obj":"gene79718"},{"id":"24895125-0#25#48#gene2908","span":{"begin":25,"end":48},"obj":"gene2908"},{"id":"24895125-0#8#15#gene79718","span":{"begin":8,"end":15},"obj":"gene79718"},{"id":"24895125-0#25#48#gene2908","span":{"begin":25,"end":48},"obj":"gene2908"},{"id":"24895125-0#122#144#diseaseC0023448","span":{"begin":122,"end":144},"obj":"diseaseC0023448"},{"id":"24895125-0#122#144#diseaseC0023449","span":{"begin":122,"end":144},"obj":"diseaseC0023449"},{"id":"24895125-0#122#144#diseaseC1961102","span":{"begin":122,"end":144},"obj":"diseaseC1961102"},{"id":"24895125-0#122#144#diseaseC0023448","span":{"begin":122,"end":144},"obj":"diseaseC0023448"},{"id":"24895125-0#122#144#diseaseC0023449","span":{"begin":122,"end":144},"obj":"diseaseC0023449"},{"id":"24895125-0#122#144#diseaseC1961102","span":{"begin":122,"end":144},"obj":"diseaseC1961102"},{"id":"24895125-0#89#114#diseaseC1841972","span":{"begin":89,"end":114},"obj":"diseaseC1841972"},{"id":"24895125-3#14#21#gene79718","span":{"begin":526,"end":533},"obj":"gene79718"},{"id":"24895125-3#76#83#gene79718","span":{"begin":588,"end":595},"obj":"gene79718"},{"id":"24895125-3#113#136#gene2908","span":{"begin":625,"end":648},"obj":"gene2908"},{"id":"24895125-3#296#301#gene8841","span":{"begin":808,"end":813},"obj":"gene8841"},{"id":"24895125-3#35#50#diseaseC1292769","span":{"begin":547,"end":562},"obj":"diseaseC1292769"}],"relations":[{"id":"8#15#gene79718122#144#diseaseC0023448","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#122#144#diseaseC0023448"},{"id":"8#15#gene79718122#144#diseaseC0023449","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#122#144#diseaseC0023449"},{"id":"8#15#gene79718122#144#diseaseC1961102","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#122#144#diseaseC1961102"},{"id":"8#15#gene79718122#144#diseaseC0023448","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#122#144#diseaseC0023448"},{"id":"8#15#gene79718122#144#diseaseC0023449","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#122#144#diseaseC0023449"},{"id":"8#15#gene79718122#144#diseaseC1961102","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#122#144#diseaseC1961102"},{"id":"8#15#gene7971889#114#diseaseC1841972","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#89#114#diseaseC1841972"},{"id":"25#48#gene2908122#144#diseaseC0023448","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#122#144#diseaseC0023448"},{"id":"25#48#gene2908122#144#diseaseC0023449","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#122#144#diseaseC0023449"},{"id":"25#48#gene2908122#144#diseaseC1961102","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#122#144#diseaseC1961102"},{"id":"25#48#gene2908122#144#diseaseC0023448","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#122#144#diseaseC0023448"},{"id":"25#48#gene2908122#144#diseaseC0023449","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#122#144#diseaseC0023449"},{"id":"25#48#gene2908122#144#diseaseC1961102","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#122#144#diseaseC1961102"},{"id":"25#48#gene290889#114#diseaseC1841972","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#89#114#diseaseC1841972"},{"id":"8#15#gene79718122#144#diseaseC0023448","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#122#144#diseaseC0023448"},{"id":"8#15#gene79718122#144#diseaseC0023449","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#122#144#diseaseC0023449"},{"id":"8#15#gene79718122#144#diseaseC1961102","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#122#144#diseaseC1961102"},{"id":"8#15#gene79718122#144#diseaseC0023448","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#122#144#diseaseC0023448"},{"id":"8#15#gene79718122#144#diseaseC0023449","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#122#144#diseaseC0023449"},{"id":"8#15#gene79718122#144#diseaseC1961102","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#122#144#diseaseC1961102"},{"id":"8#15#gene7971889#114#diseaseC1841972","pred":"associated_with","subj":"24895125-0#8#15#gene79718","obj":"24895125-0#89#114#diseaseC1841972"},{"id":"25#48#gene2908122#144#diseaseC0023448","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#122#144#diseaseC0023448"},{"id":"25#48#gene2908122#144#diseaseC0023449","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#122#144#diseaseC0023449"},{"id":"25#48#gene2908122#144#diseaseC1961102","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#122#144#diseaseC1961102"},{"id":"25#48#gene2908122#144#diseaseC0023448","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#122#144#diseaseC0023448"},{"id":"25#48#gene2908122#144#diseaseC0023449","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#122#144#diseaseC0023449"},{"id":"25#48#gene2908122#144#diseaseC1961102","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#122#144#diseaseC1961102"},{"id":"25#48#gene290889#114#diseaseC1841972","pred":"associated_with","subj":"24895125-0#25#48#gene2908","obj":"24895125-0#89#114#diseaseC1841972"},{"id":"14#21#gene7971835#50#diseaseC1292769","pred":"associated_with","subj":"24895125-3#14#21#gene79718","obj":"24895125-3#35#50#diseaseC1292769"},{"id":"76#83#gene7971835#50#diseaseC1292769","pred":"associated_with","subj":"24895125-3#76#83#gene79718","obj":"24895125-3#35#50#diseaseC1292769"},{"id":"113#136#gene290835#50#diseaseC1292769","pred":"associated_with","subj":"24895125-3#113#136#gene2908","obj":"24895125-3#35#50#diseaseC1292769"},{"id":"296#301#gene884135#50#diseaseC1292769","pred":"associated_with","subj":"24895125-3#296#301#gene8841","obj":"24895125-3#35#50#diseaseC1292769"}],"attributes":[{"subj":"24895125-0#8#15#gene79718","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-0#25#48#gene2908","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-0#8#15#gene79718","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-0#25#48#gene2908","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-0#122#144#diseaseC0023448","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-0#122#144#diseaseC0023449","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-0#122#144#diseaseC1961102","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-0#122#144#diseaseC0023448","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-0#122#144#diseaseC0023449","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-0#122#144#diseaseC1961102","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-0#89#114#diseaseC1841972","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-3#14#21#gene79718","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-3#76#83#gene79718","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-3#113#136#gene2908","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-3#296#301#gene8841","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"24895125-3#35#50#diseaseC1292769","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":89,"end":114},"obj":"Disease"},{"id":"T2","span":{"begin":122,"end":144},"obj":"Disease"},{"id":"T4","span":{"begin":211,"end":249},"obj":"Disease"},{"id":"T5","span":{"begin":547,"end":562},"obj":"Disease"},{"id":"T6","span":{"begin":1173,"end":1198},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0014421"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0001018"},{"id":"A3","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0004967"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0000870"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0020511"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0014421"},{"subj":"T1","pred":"source","obj":"mondo_disease"},{"subj":"T2","pred":"source","obj":"mondo_disease"},{"subj":"T4","pred":"source","obj":"mondo_disease"},{"subj":"T5","pred":"source","obj":"mondo_disease"},{"subj":"T6","pred":"source","obj":"mondo_disease"}]},{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":136,"end":144},"obj":"Phenotype"},{"id":"T2","span":{"begin":221,"end":249},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0001909"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0006721"},{"subj":"T1","pred":"source","obj":"HP-phenotype"},{"subj":"T2","pred":"source","obj":"HP-phenotype"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}]},{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":120,"end":135},"obj":"Cell"},{"id":"T2","span":{"begin":227,"end":240},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0017006"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0017005"},{"subj":"T1","pred":"source","obj":"CL-cell"},{"subj":"T2","pred":"source","obj":"CL-cell"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubmedHPO","color":"#ec93dd","default":true},{"id":"DisGeNET","color":"#93ece0"},{"id":"sentences","color":"#ecc693"},{"id":"DisGeNet-2017-sample","color":"#ac93ec"},{"id":"DisGeNET5_gene_disease","color":"#93ec93"},{"id":"mondo_disease","color":"#ec93ad"},{"id":"HP-phenotype","color":"#93c7ec"},{"id":"CL-cell","color":"#e1ec93"}]}]}}