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KMID : 0366220150500040235
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Korean Journal of Hematology
2015 Volume.50 No. 4 p.235 ~ p.241
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The prognostic value of glucocorticoid receptors for adult acute lymphoblastic leukemia
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Ahmed M. L. Bedewy
Shereen M. EL-Maghraby
Noha S. Kandil
Waleed R. El-Bendary
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Abstract
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Background: Therapeutic protocols used in adult acute lymphoblastic leukemia (ALL) are widely variable, and glucocorticoids (GCs) are essential components in ALL treatment. Therefore, this study aimed to evaluate the distribution of prominent glucocorticoid receptor (GR) gene polymorphic variants among adult ALL patients. We also investigated the association between GR messenger ribonucleic acid (mRNA) isoform expressions and the response to chemotherapy.
Methods: Fifty-two newly diagnosed Philadelphia-negative adult ALL patients and 30 healthy control subjects were enrolled in this study. Genotyping was carried out using a polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. GR mRNA isoform expressions were assayed by quantitative real-time PCR.
Results: ALL patients in this study had a median age of 34 years (range, 18?75). GRα expression was associated with complete remission (P=0.03), while GRγ mRNA expression was significantly higher in GC resistant patients (P=0.032) and in non-responders (P=0.019). However, there were no significant associations with GC resistance. The BclI polymorphic variant of the GR gene was the most frequent in adult ALL patients and was not associated with the GC response. Both higher GRα expression and lower GRγ expression were associated with achievement of complete remission, while higher GRγ expression was associated with GC-resistance.
Conclusion: Our data suggest that the level of GR isoform expression may be useful in predicting GC response, achievement of complete remission, and better event-free survival in ALL patients. However, further evaluation with a larger cohort of patients is warranted.
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KEYWORD
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Glucocorticoid receptor, Genetic polymorphism, Acute lymphoblastic leukemia
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