title: Differential mRNA expression of glucocorticoid receptor alpha and beta is associated with glucocorticoid sensitivity of acute lymphoblastic leukemia in children.
abstract: BACKGROUND
  Sensitivity of leukemic blasts to glucocorticoid is one of the important prognostic factors for pediatric acute lymphoblastic leukemia (ALL). Alternative splicing of the glucocorticoid receptor (GR) gene results in several isoforms. We examined an association of the expression pattern of GR isoforms in leukemic blasts with their sensitivity to glucocorticoid in childhood ALL.
  
  
  METHODS
  The relative mRNA expression of GRalpha, GRbeta, GRgamma, and GR-P was determined in leukemic blasts of 23 childhood ALL at initial presentation and of 14 ALL cell lines by quantitative RT-PCR. Glucocorticoid-sensitivity of leukemic blasts was determined by counting apoptotic cells with flow cytometry after 6-hr incubation with prednisolone (PSL).
  
  
  RESULTS
  The relative expression of GRalpha mRNA was significantly higher in blasts of B-precursor ALL than those of others (13.6 vs. 2.24, P = 0.015), while those of GRalpha, GRbeta, and GRgamma showed no difference. GRbeta/GRalpha ratios were significantly lower in B-precursor ALL than others (0.80 vs. 4.64, P = 0.035). The proportions of apoptotic cells after PSL exposure were inversely correlated with the GRbeta/GRalpha ratios in ALL cell lines (r = -0.612, P = 0.020). PSL administration induced apoptosis efficiently in leukemic blasts with low GRbeta/GRalpha ratios compared with those of high ratios (cell lines: 4.93% vs. 1.90%, P = 0.013, primary leukemia: 11.7% vs. 3.6%, P = 0.037).
  
  
  CONCLUSIONS
  The amounts of GR isoform mRNA in leukemic blasts were closely correlated with sensitivity to glucocorticoid exposure. The mRNA expression pattern of GR isoforms at initial presentation may provide valuable information for prognosis in children with newly diagnosed ALL.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. yuuki-k@pediatr.med.kyushu-u.ac.jp
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Koga
authors.forename: Akinobu
authors.initials: A
authors.lastname: Matsuzaki
authors.forename: Aiko
authors.initials: A
authors.lastname: Suminoe
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Hattori
authors.forename: Satomi
authors.initials: S
authors.lastname: Kanemitsu
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D000293:Adolescent; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000276:immunology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D011379:Prognosis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured
chemical_list: D018931:Antineoplastic Agents, Hormonal; D005938:Glucocorticoids; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011965:Receptors, Glucocorticoid