Polymorphisms in glucocorticoid receptor gene and the outcome of childhood acute lymphoblastic leukemia (ALL)

Labuda, Malgorzata; Gahier, Annabel; Gagné, Vincent; Moghrabi, Albert; Sinnett, Daniel; Krajinovic, Maja

doi:10.1016/j.leukres.2009.08.007

« Previous Next »Leukemia Research
Volume 34, Issue 4 , Pages 492-497, April 2010

Polymorphisms in glucocorticoid receptor gene and the outcome of childhood acute lymphoblastic leukemia (ALL)

Malgorzata Labuda
- Centre de recherche Charles Bruneau, Montréal, Québec, Canada
Annabel Gahier
- Centre de recherche Charles Bruneau, Montréal, Québec, Canada
Vincent Gagné
- Centre de recherche Charles Bruneau, Montréal, Québec, Canada
Albert Moghrabi
- Centre de recherche Charles Bruneau, Montréal, Québec, Canada
- Centre de Recherche, Centre hospitalier universitaire Sainte-Justine, Département de Pédiatrie, Montréal, Québec, Canada
Daniel Sinnett
- Centre de recherche Charles Bruneau, Montréal, Québec, Canada
- Centre de Recherche, Centre hospitalier universitaire Sainte-Justine, Département de Pédiatrie, Montréal, Québec, Canada
Maja Krajinovic
- Centre de recherche Charles Bruneau, Montréal, Québec, Canada
- Centre de Recherche, Centre hospitalier universitaire Sainte-Justine, Département de Pédiatrie, Montréal, Québec, Canada
- Département de pharmacologie, Université de Montréal, Montréal, Québec, Canada
- Corresponding author at: Centre de recherche, Hôpital Sainte-Justine, 3175 Côte-Ste-Catherine, Montréal, Québec, H3T 1C5 Canada. Tel.: +1 514 345 4931x6259; fax: +1 514 345 4731.

Received 26 May 2009; received in revised form 31 July 2009; accepted 8 August 2009. published online 07 March 2011.

Abstract

Childhood acute lymphoblastic leukemia patients (n=310) were analyzed for four SNPs in the NR3C1 gene. Polymorphisms −627A/G, intron 2 +646C/G and 9bT/C were all associated with reduced event-free survival. Haplotypes composed of AGT alleles at these loci and tagged by the intron 2 +646G variant also associated with lower event-free survival (p=0.03). The progressive impact of this haplotype on outcome was seen with two copies associated with reduced overall survival (p=0.05). Quantitative mRNA analysis in lymphoblastoid cell lines showed that carriers of the AGT haplotype had a higher ratio of GR γ/α isoforms (p=0.04), which possibly explains its association with reduced event-free survival and overall survival.