Differential mRNA expression of glucocorticoid receptor α and β is associated with glucocorticoid sensitivity of acute lymphoblastic leukemia in children

Yuhki Koga, Akinobu Matsuzaki, Aiko Suminoe, Hiroyoshi Hattori, Satomi Kanemitsu, Toshiro Hara

Research output: Contribution to journalArticle

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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. Procedures. The relative mRNA expression of GRα, GRβ, GRγ, 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 GRα 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 GRα, GRβ, and GRγ showed no difference. GRβ/GRα 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 GRβ/GRα ratios in ALL cell lines (r = -0.612, P=0.020). PSL administration induced apoptosis efficiently in leukemic blasts with low GRβ/GRα 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.

Original languageEnglish
Pages (from-to)121-127
Number of pages7
JournalPediatric Blood and Cancer
Volume45
Issue number2
DOIs
Publication statusPublished - Aug 1 2005

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Glucocorticoid Receptors
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Glucocorticoids
Messenger RNA
Prednisolone
Protein Isoforms
Cell Line
RNA Isoforms
Alternative Splicing

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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Differential mRNA expression of glucocorticoid receptor α and β is associated with glucocorticoid sensitivity of acute lymphoblastic leukemia in children. / Koga, Yuhki; Matsuzaki, Akinobu; Suminoe, Aiko; Hattori, Hiroyoshi; Kanemitsu, Satomi; Hara, Toshiro.

In: Pediatric Blood and Cancer, Vol. 45, No. 2, 01.08.2005, p. 121-127.

Research output: Contribution to journalArticle

Koga, Yuhki ; Matsuzaki, Akinobu ; Suminoe, Aiko ; Hattori, Hiroyoshi ; Kanemitsu, Satomi ; Hara, Toshiro. / Differential mRNA expression of glucocorticoid receptor α and β is associated with glucocorticoid sensitivity of acute lymphoblastic leukemia in children. In: Pediatric Blood and Cancer. 2005 ; Vol. 45, No. 2. pp. 121-127.
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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. Procedures. The relative mRNA expression of GRα, GRβ, GRγ, 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 GRα 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 GRα, GRβ, and GRγ showed no difference. GRβ/GRα 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 GRβ/GRα ratios in ALL cell lines (r = -0.612, P=0.020). PSL administration induced apoptosis efficiently in leukemic blasts with low GRβ/GRα 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.",
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AU - Koga, Yuhki

AU - Matsuzaki, Akinobu

AU - Suminoe, Aiko

AU - Hattori, Hiroyoshi

AU - Kanemitsu, Satomi

AU - Hara, Toshiro

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N2 - 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. Procedures. The relative mRNA expression of GRα, GRβ, GRγ, 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 GRα 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 GRα, GRβ, and GRγ showed no difference. GRβ/GRα 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 GRβ/GRα ratios in ALL cell lines (r = -0.612, P=0.020). PSL administration induced apoptosis efficiently in leukemic blasts with low GRβ/GRα 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.

AB - 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. Procedures. The relative mRNA expression of GRα, GRβ, GRγ, 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 GRα 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 GRα, GRβ, and GRγ showed no difference. GRβ/GRα 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 GRβ/GRα ratios in ALL cell lines (r = -0.612, P=0.020). PSL administration induced apoptosis efficiently in leukemic blasts with low GRβ/GRα 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.

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