Blood Res.  2015 Dec;50(4):235-241. 10.5045/br.2015.50.4.235.

The prognostic value of glucocorticoid receptors for adult acute lymphoblastic leukemia

• Bedewy AM
• EL-Maghraby SM
• Kandil NS
• El-Bendary WR

• KMID: 2133758
• DOI: http://doi.org/10.5045/br.2015.50.4.235

Abstract

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). GRalpha expression was associated with complete remission (P=0.03), while GRgamma 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 GRalpha expression and lower GRgamma expression were associated with achievement of complete remission, while higher GRgamma 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.

Keyword

Glucocorticoid receptor; Genetic polymorphism; Acute lymphoblastic leukemia

MeSH Terms

Adult*
Cohort Studies
Disease-Free Survival
Drug Therapy
Glucocorticoids
Humans
Polymerase Chain Reaction
Polymorphism, Genetic
Precursor Cell Lymphoblastic Leukemia-Lymphoma*
Real-Time Polymerase Chain Reaction
Receptors, Glucocorticoid*
RNA
RNA, Messenger
Glucocorticoids
RNA
RNA, Messenger
Receptors, Glucocorticoid

Figure

• 

  Fig. 1 (A) Lanes 1-4 represent polymerase chain reaction (PCR) products for BclI polymorphism from 4 acute lymphoblastic leukemia (ALL) patients (335 base pairs (bp)). (B) Restriction fragment length polymorphism-digested PCR products for BclI polymorphism from ALL patients. Lanes 1 and 2 represent restriction fragments of PCR products for ALL patients with the CC genotype (222, 117 bp). Lanes 3 and 4 represent restriction PCR products for ALL patients with the CG genotype (335, 222, 117 bp). (C) Lanes 1-4 represent PCR products for N363S polymorphism from ALL patients (248 bp). Lane M represents the 100 bp ladder marker.

• 

  Fig. 2 Kaplan-Meier chart showing event-free survival for the BclI genotype (A), the N363S genotype (B), and the α/β isoform expression ratio (C).

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