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Glucocorticoid receptor alpha, beta and gamma expression vs in vitro glucocorticod resistance in childhood leukemia

Leukemia volume 18, pages 530–537 (2004)Cite this article

Abstract

Alternative splicing of the primary glucocorticoid receptor (GR) transcript, resulting in glucocorticoid receptor alpha GRα, glucocorticoid receptor beta GRβ and glucocorticoid receptor gamma GRγ, may influence glucocorticoid (GC) resistance in childhood leukemia. To test this hypothesis, we determined GRα/β protein and GRα/β/γ mRNA expression levels in 43 initial acute lymphoblastic leukemia (iALL), 10 initial myeloid leukemia (iAML), 11 relapsed ALL (rALL) samples and one rAML sample. The results were correlated with in vitro GC resistance. GRα mRNA correlated with protein expression (ρ=0.39–0.56, P<0.05), but the protein to mRNA ratio was median 2.2-fold lower in rALL than in iALL (P<0.05). GRβ mRNA was median 137-fold lower than GRα mRNA and correlated with GRα mRNA expression (ρ=0.71, P<0.0001). GRβ could not be detected at the protein level. GRγ accounted for a median of 2.8% (range 0.95–7.4%) of all GR transcripts. GRα (protein and mRNA) and GRβ (mRNA) expressions or GRα/GRβ ratios did not correlate with in vitro GC resistance in iALL, but GRγ (mRNA) did (ρ=0.52, P=0.007). These results suggest that GRβ is not involved in GC resistance in childhood leukemia. The association between GRγ expression and in vitro GC resistance in iALL and the decreased protein/mRNA ratio in rALL, a subgroup resistant to GCs, warrants further exploration.

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Acknowledgements

This work was supported by a grant from the Dutch Cancer Society (VU 97-1564) and the European Commission (EUGIA). We are especially grateful to Dr LJ van‘t Veer from the Netherlands Cancer Institute (Amsterdam) and Dr. JP Meijerink from the Sophia Children's Hospital (Rotterdam) for their many helpful suggestions. In addition, we would like express our gratitude to Dr JC Willey from the medical college of Ohio (USA) for his help in the design of the primers for the CT-RT-PCR. We also thank AJF Broekhuizen, DR Huismans, AH Loonen and CH van Zantwijk for their excellent technical assistance. Finally, we thank the members of the board of the DCOG: H van den Berg, JPM Bökkerink, SSN de Graaf, B Granzen, PM Hoogerbrugge, WA Kamps, FAE Nabben, R Pieters, JA Rammeloo, T Révész and AJP Veerman.

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Authors and Affiliations

  1. Department of Pediatric Hematology/Oncology, VU University Medical Center, De Boelelaan, Amsterdam, The Netherlands

    E G Haarman, G J L Kaspers, M M A Rottier & A J P Veerman

  2. Department of Pediatric Hematology/Oncology, University Hospital/Sophia Children's Hospital, Dr Molewaterplein, Rotterdam, The Netherlands

    R Pieters

  3. Dutch Childhood Oncology Group, The Hague, The Netherlands

    R Pieters & A J P Veerman

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  1. E G Haarman
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Correspondence to E G Haarman.

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Haarman, E., Kaspers, G., Pieters, R. et al. Glucocorticoid receptor alpha, beta and gamma expression vs in vitro glucocorticod resistance in childhood leukemia. Leukemia 18, 530–537 (2004). https://doi.org/10.1038/sj.leu.2403225

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