{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:47:48Z","timestamp":1773028068479,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T00:00:00Z","timestamp":1503964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"JSPS KAKENHI","award":["15K09645"],"award-info":[{"award-number":["15K09645"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glucocorticoid (GC) shows antileukaemic activity via binding to the GC receptor (GR). The human <jats:italic>GR<\/jats:italic> gene has 4 splicing variants besides the functional isoform GR\u03b1, but their significance in GC sensitivity of acute lymphoblastic leukaemia (ALL) has been inconsistent. Additionally, several studies evaluated the relevance of <jats:italic>GR<\/jats:italic> gene single nucleotide polymorphisms (SNPs) in the GC sensitivity of ALL, but the current cumulative evidence appears inconclusive. Addressing limitations in previous studies, we used a large series of B\u2010cell precursor ALL (BCP\u2010ALL) cell lines established from Japanese patients to comprehensively examine all 5 splicing variants of the <jats:italic>GR<\/jats:italic> gene and candidate SNPs, and their association with GC\u2010sensitivity. We performed real\u2010time reverse transcription polymerase chain reaction (RT\u2010PCR) analyses with 10 sets of primers that differentially quantify the 5 isoforms in different combinations, and the strongest correlations with GC sensitivity were observed for the real\u2010time RT\u2010PCR of exons 7 and 8 (prednisolone sensitivity; <jats:italic>r<\/jats:italic>\u00a0=\u00a0\u22120.534, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.29, <jats:italic>P<\/jats:italic>\u00a0=\u00a01.4\u00a0\u00d7\u00a010<jats:sup>\u22126<\/jats:sup>) and exons 8 and 9a (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u22120.583, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.34, <jats:italic>P<\/jats:italic>\u00a0=\u00a07.6\u00a0\u00d7\u00a010<jats:sup>\u22128<\/jats:sup>), both specific for <jats:italic>GR\u03b1<\/jats:italic> and <jats:italic>GR\u03b3<\/jats:italic> isoforms. In contrast, the real\u2010time RT\u2010PCR of junction of exons 3g and 4 and exon 4, specific for <jats:italic>GR\u03b3<\/jats:italic> isoform alone, did not show significant correlation with GC sensitivity (prednisolone sensitivity; <jats:italic>r<\/jats:italic>\u00a0=\u00a0\u22120.403, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.16, <jats:italic>P<\/jats:italic>\u00a0=\u00a04.6\u00a0\u00d7\u00a010<jats:sup>\u22124<\/jats:sup>). These observations are consistent with the notion that <jats:italic>GR\u03b1<\/jats:italic> plays a central role in the GC\u2010mediated proapoptotic activity in BCP\u2010ALL. In addition, a promoter region SNP genotype (rs72555796) showed a significant association with GC sensitivity (prednisolone sensitivity; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.010) and tended to show an association with <jats:italic>GR<\/jats:italic> gene expression (RT\u2010PCR of exons 7 and 8; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.170). These findings indicate that isoform profiles and SNP genotypes of the <jats:italic>GR<\/jats:italic> gene may be useful indicators of GC sensitivity in BCP\u2010ALL.<\/jats:p>","DOI":"10.1002\/hon.2471","type":"journal-article","created":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T15:10:51Z","timestamp":1504019451000},"page":"245-251","source":"Crossref","is-referenced-by-count":6,"title":["Splicing variant profiles and single nucleotide polymorphisms of the glucocorticoid receptor gene in relation to glucocorticoid sensitivity of <scp>B<\/scp>\u2010cell precursor acute lymphoblastic leukaemia"],"prefix":"10.1002","volume":"36","author":[{"given":"Meixian","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, School of Medicine University of Yamanashi  Chuo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4783-2184","authenticated-orcid":false,"given":"Takeshi","family":"Inukai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine University of Yamanashi  Chuo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko","family":"Kagami","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine University of Yamanashi  Chuo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masako","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine University of Yamanashi  Chuo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamao","family":"Shinohara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine University of Yamanashi  Chuo 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Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Goto","sequence":"additional","affiliation":[{"name":"Hematology\/Oncology &amp; Regenerative Medicine Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayoshi","family":"Minegishi","sequence":"additional","affiliation":[{"name":"Tohoku Block Center, Japanese Red Cross Society  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shotaro","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Mie University Graduate School of Medicine  Tsu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin Y.","family":"Urayama","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology St Luke's International University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanji","family":"Sugita","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine University of Yamanashi  Chuo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,8,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.09.007"},{"issue":"14","key":"e_1_2_7_3_1","first-page":"3276","article-title":"Glucocorticoid receptor structure and function in glucocorticoid\u2010resistant small cell lung carcinoma cells","volume":"56","author":"Ray DW","year":"1996","journal-title":"Cancer Res"},{"issue":"1","key":"e_1_2_7_4_1","first-page":"99","article-title":"Two naturally\u2010occurring isoforms and their expression of a glucocorticoid receptor gene from an androgen\u2010dependent mouse tumor","volume":"274","author":"Kasai Y","year":"1990","journal-title":"FEBS 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