Protein expression of the glucocorticoid receptor in childhood acute lymphoblastic leukemia

Hannover Medical School, Pediatric Hematology and Oncology, 30625 Hannover, Germany. lauten.melchior@mh-hannover.de

BACKGROUND AND OBJECTIVES: Early treatment response is a strong predictor for treatment outcome in childhood acute lymphoblastic leukemia (ALL), treated within the protocols of the Berlin-Frankfurt-Munster (BFM) study group. In the ALL-BFM trials, early treatment response is assessed by in vivo response to glucocorticoids (prednisone response), the molecular background of which is unknown. Initial in vivo resistance to glucocorticoid (GC) treatment in childhood ALL (prednisone-poor response) is associated with a dramatically shorter event-free survival than that found in GC-sensitive patients (prednisone-good responders). The intracellular effects of glucocorticoids are mediated by the glucocorticoid receptor (GR). The protein expression of the GR has been linked to in vivo and in vitro GC resistance in various diseases treated with GC. However, existing data are conflicting. RESULTS: DESIGN AND METHODS: We performed a case-control study for prednisone response to investigate the association of in vivo GC resistance and GR protein expression in childhood ALL. GR expression was assessed using Western blot technology. RESULTS: The median relative GR protein expression of all patients was 0.87. Overall, we did not find different GR protein expression in PPR and PGR patients. GR protein expression was 0.91 in PGR patients versus 0.85 in PPR ones of in vivo GC resistance and GR expression. INTERPRETATION AND CONCLUSIONS: We conclude that the expression of GR is of minor importance for in vivo GC resistance in childhood ALL.

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