Expression of heat-shock protein 90 in glucocorticoid-sensitive and -resistant childhood acute lymphoblastic leukaemia.
Early reduction of leukaemic cells by chemotherapy is a strong predictor for treatment outcome in childhood acute lymphoblastic leukaemia (ALL). In ALL-(Berlin-Frankfurt-Münster) trials, early treatment response is assessed by the in vivo response to glucocorticoids (prednisone response, PR), the molecular background of which is unknown. The intracellular effects of glucocorticoids (GCs) are mediated by the glucocorticoid receptor (GR). In the absence of GC, the inactive GR resides within a multiprotein complex, consisting predominantly of the chaperone protein hsp90 (heat-shock protein 90). Until now, studies targeting GC resistance mainly focused on GR disorders and alterations of genes known to be associated with drug resistance. In addition, the GR multiprotein complex was associated with GC resistance in in vitro studies. We performed a case-control study for PR to investigate the association of in vivo GC resistance and hsp90 expression in childhood ALL. Hsp90 expression was assessed using a real-time PCR approach (Taqman technology) and Western blot technology. In this setting, we found no association of in vivo GC resistance and hsp90 expression. Therefore, we conclude that the expression of hsp90, the major component of the GR activating complex, is of minor importance for the in vivo GC resistance in childhood ALL.
Lauten
M
M
Hannover Medical School, Paediatric Haematology and Oncology, Hannover, Germany.
Beger
C
C
Gerdes
K
K
Asgedom
G
G
Kardinal
C
C
Welte
K
K
Schrappe
M
M
D000293:Adolescent; D015153:Blotting, Western; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011241:Prednisone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005938:Glucocorticoids; D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger; D011241:Prednisone