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Article: Lymphocyte-Specific Chromatin Accessibility Pre-determines Glucocorticoid Resistance in Acute Lymphoblastic Leukemia

TitleLymphocyte-Specific Chromatin Accessibility Pre-determines Glucocorticoid Resistance in Acute Lymphoblastic Leukemia
Authors
Keywordsacute lymphoblastic leukemia
chromatin accessibility
drug resistance
enhancer
epigenetics
glucocorticoid
lymphocyte specificity
patient-derived xenograft, PDX
Issue Date2018
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/ccell
Citation
Cancer Cell, 2018, v. 34 n. 6, p. 906-921.e8 How to Cite?
AbstractGlucocorticoids play a critical role in the treatment of lymphoid malignancies. While glucocorticoid efficacy can be largely attributed to lymphocyte-specific apoptosis, its molecular basis remains elusive. Here, we studied genome-wide lymphocyte-specific open chromatin domains (LSOs), and integrated LSOs with glucocorticoid-induced RNA transcription and chromatin modulation using an in vivo patient-derived xenograft model of acute lymphoblastic leukemia (ALL). This led to the identification of LSOs critical for glucocorticoid-induced apoptosis. Glucocorticoid receptor cooperated with CTCF at these LSOs to mediate DNA looping, which was inhibited by increased DNA methylation in glucocorticoid-resistant ALL and non-lymphoid cell types. Our study demonstrates that lymphocyte-specific epigenetic modifications pre-determine glucocorticoid resistance in ALL and may account for the lack of glucocorticoid sensitivity in other cell types.
Persistent Identifierhttp://hdl.handle.net/10722/267380
ISSN
2023 Impact Factor: 48.8
2023 SCImago Journal Rankings: 17.507
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJing, D-
dc.contributor.authorHuang, Y-
dc.contributor.authorLiu, X-
dc.contributor.authorSia, KCS-
dc.contributor.authorZhang, JC-
dc.contributor.authorTai, X-
dc.contributor.authorWang, M-
dc.contributor.authorToscan, CE-
dc.contributor.authorMcCalmont, H-
dc.contributor.authorEvans, K-
dc.contributor.authorMayoh, C-
dc.contributor.authorPoulos, RC-
dc.contributor.authorSpan, M-
dc.contributor.authorMi, J-
dc.contributor.authorZhang, C-
dc.contributor.authorWong, WHJ-
dc.contributor.authorBeck, D-
dc.contributor.authorPimanda, JE-
dc.contributor.authorLock, RB-
dc.date.accessioned2019-02-18T09:00:49Z-
dc.date.available2019-02-18T09:00:49Z-
dc.date.issued2018-
dc.identifier.citationCancer Cell, 2018, v. 34 n. 6, p. 906-921.e8-
dc.identifier.issn1535-6108-
dc.identifier.urihttp://hdl.handle.net/10722/267380-
dc.description.abstractGlucocorticoids play a critical role in the treatment of lymphoid malignancies. While glucocorticoid efficacy can be largely attributed to lymphocyte-specific apoptosis, its molecular basis remains elusive. Here, we studied genome-wide lymphocyte-specific open chromatin domains (LSOs), and integrated LSOs with glucocorticoid-induced RNA transcription and chromatin modulation using an in vivo patient-derived xenograft model of acute lymphoblastic leukemia (ALL). This led to the identification of LSOs critical for glucocorticoid-induced apoptosis. Glucocorticoid receptor cooperated with CTCF at these LSOs to mediate DNA looping, which was inhibited by increased DNA methylation in glucocorticoid-resistant ALL and non-lymphoid cell types. Our study demonstrates that lymphocyte-specific epigenetic modifications pre-determine glucocorticoid resistance in ALL and may account for the lack of glucocorticoid sensitivity in other cell types.-
dc.languageeng-
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/ccell-
dc.relation.ispartofCancer Cell-
dc.subjectacute lymphoblastic leukemia-
dc.subjectchromatin accessibility-
dc.subjectdrug resistance-
dc.subjectenhancer-
dc.subjectepigenetics-
dc.subjectglucocorticoid-
dc.subjectlymphocyte specificity-
dc.subjectpatient-derived xenograft, PDX-
dc.titleLymphocyte-Specific Chromatin Accessibility Pre-determines Glucocorticoid Resistance in Acute Lymphoblastic Leukemia-
dc.typeArticle-
dc.identifier.emailWong, WHJ: jwhwong@hku.hk-
dc.identifier.authorityWong, WHJ=rp02363-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.ccell.2018.11.002-
dc.identifier.scopuseid_2-s2.0-85056855732-
dc.identifier.hkuros296873-
dc.identifier.volume34-
dc.identifier.issue6-
dc.identifier.spage906-
dc.identifier.epage921.e8-
dc.identifier.isiWOS:000452614700007-
dc.publisher.placeUnited States-
dc.identifier.issnl1535-6108-

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