The prognostic value of glucocorticoid receptors for adult acute lymphoblastic leukemia

被引:7
作者
Bedewy, Ahmed M. L. [1 ]
El-Maghraby, Shereen M. [1 ]
Kandil, Noha S. [2 ]
El-Bendary, Waleed R. [3 ]
机构
[1] Alexandria Univ, Med Res Inst, Hematol Dept, 8 Mahmoud Younes St, Alexandria 21615, Egypt
[2] Alexandria Univ, Med Res Inst, Chem Pathol Dept, Alexandria, Egypt
[3] Mil Med Acad, Dept Clin Pathol, Cairo, Egypt
关键词
Glucocorticoid receptor; Genetic polymorphism; Acute lymphoblastic leukemia;
D O I
10.5045/br.2015.50.4.235
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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). GR alpha expression was associated with complete remission (P=0.03), while GR gamma 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 GR alpha expression and lower GR gamma expression were associated with achievement of complete remission, while higher GR gamma 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.
引用
收藏
页码:235 / 241
页数:7
相关论文
共 26 条
  • [1] Pharmacogenetic determinants of outcome in acute lymphoblastic leukaemia
    Aplenc, R
    Lange, B
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 2004, 125 (04) : 421 - 434
  • [2] Glucocorticoid receptor polymorphisms and post-traumatic stress disorder
    Bachmann, AW
    Sedgley, TL
    Jackson, RV
    Gibson, JN
    Young, RMD
    Torpy, DJ
    [J]. PSYCHONEUROENDOCRINOLOGY, 2005, 30 (03) : 297 - 306
  • [3] Baxter J D, 2000, Adv Intern Med, V45, P317
  • [4] Expression and structural analysis of glucocorticoid receptor isoform gamma in human leukaemia cells using an isoform-specific real-time polymerase chain reaction approach
    Beger, C
    Gerdes, K
    Lauten, M
    Tissing, WJE
    Fernandez-Munoz, I
    Schrappe, M
    Welte, K
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 2003, 122 (02) : 245 - 252
  • [5] Characterization of the BclI polymorphism in the glucocorticoid receptor gene
    Fleury, I
    Beau-Lieu, P
    Primeau, M
    Labuda, D
    Sinnett, D
    Krajinovic, M
    [J]. CLINICAL CHEMISTRY, 2003, 49 (09) : 1528 - 1531
  • [6] Gerdes K, 2001, BLOOD ASH ANN M AB S, V98
  • [7] Glucocorticoid receptor alpha, beta and gamma expression vs in vitro glucocorticod resistance in childhood leukemia
    Haarman, EG
    Kaspers, GJL
    Pieters, R
    Rottier, MMA
    Veerman, AJP
    [J]. LEUKEMIA, 2004, 18 (03) : 530 - 537
  • [8] PRIMARY STRUCTURE AND EXPRESSION OF A FUNCTIONAL HUMAN GLUCOCORTICOID RECEPTOR CDNA
    HOLLENBERG, SM
    WEINBERGER, C
    ONG, ES
    CERELLI, G
    ORO, A
    LEBO, R
    THOMPSON, EB
    ROSENFELD, MG
    EVANS, RM
    [J]. NATURE, 1985, 318 (6047) : 635 - 641
  • [9] Pediatric-Inspired Therapy in Adults With Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: The GRAALL-2003 Study
    Huguet, Francoise
    Leguay, Thibaut
    Raffoux, Emmanuel
    Thomas, Xavier
    Beldjord, Kheira
    Delabesse, Eric
    Chevallier, Patrice
    Buzyn, Agnes
    Delannoy, Andre
    Chalandon, Yves
    Vernant, Jean-Paul
    Lafage-Pochitaloff, Marina
    Chassevent, Agnes
    Lheritier, Veronique
    Macintyre, Elizabeth
    Bene, Marie-Christine
    Ifrah, Norbert
    Dombret, Herve
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (06) : 911 - 918
  • [10] A polymorphism in the glucocorticoid receptor gene may be associated with an increased sensitivity to glucocorticoids in vivo
    Huizenga, NATM
    Koper, JW
    De Lange, P
    Pols, HAP
    Stolk, RP
    Burger, H
    Grobbee, DE
    Brinkmann, AO
    De Jong, FH
    Lamberts, SWJ
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (01) : 144 - 151