Blood, 1 August 2006, Vol. 108, No. 3, pp. 1045-1049.
Prepublished online as a Blood First Edition Paper on March 30, 2006; DOI 10.1182/blood-2006-01-0261.
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Submitted January 20, 2006
Accepted March 16, 2006
Glucocorticoid-induced glucocorticoid receptor expression and promoter-usage is not linked to glucocorticoid resistance in childhood ALL
Wim J Tissing, Jules P Meijerink*, Bas Brinkhof, Mathilde J Broekhuis, Renee X Menezes, Monique L den Boer, and Rob Pieters
Dept of Pediatric Oncology / Hematology, ErasmusMC - Sophia Childrens Hospital, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands; Dept of Pediatric Oncology / Hematology, University of Groningen and University Medical Center Groningen, Beatrix Childrens Hospital, Groningen, The Netherlands
Dept of Pediatric Oncology / Hematology, ErasmusMC - Sophia Childrens Hospital, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
Dept of Pediatric Oncology / Hematology, ErasmusMC - Sophia Childrens Hospital, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands; Dept of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands
* Corresponding author; email: j.p.p.meijerink{at}erasmusmc.nl.
Glucocorticoid (GC) resistance is an adverse prognostic factor in childhood ALL, but little is known about causes of GC resistance. Upregulation of the glucocorticoid receptor (GR) has been suggested as an essential step to the induction of apoptosis in leukemic cells. In this study we investigated whether base-line mRNA expression levels of the five different GR promoters transcripts (1A1, 1A2, 1A3, 1B and 1C) or differences in the degree of regulation of the GR or GR promoter transcripts upon GC exposure are related to GC resistance.
Therefore, mRNA levels of the five GR promoter transcripts and of the GR were measured by quantitative real-time RT-PCR (Taqman) technology in primary ALL cells prior to and after 3, 8 and 24 hours of prednisolone exposure.
GR expression is induced upon GC exposure in primary ALL patient samples, which is opposite to what is found in tissues in which GCs do not induce apoptosis. GC resistance in childhood ALL can not be attributed to an inability of resistant cells to upregulate the expression of the GR upon GC exposure, nor to differences in GR promoter usage (at base-line and upon GC exposure).
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