Circumvention of glucocorticoid resistance in childhood leukemia.
In this study, we determined if in vitro resistance to prednisolone and dexamethasone could be circumvented by cortivazol or methylprednisolone, or reversed by meta-iodobenzylguanidine in pediatric lymphoblastic and myeloid leukemia. As there were strong correlations between the LC50 values (drug concentration inducing 50% leukemic cell kill, LCK) of the different glucocorticoids and median prednisolone/methylprednisolone, prednisolone/dexamethasone and prednisolone/cortivazol LC50 ratios did not differ between the leukemia subtypes, we conclude that none of the glucocorticoids had preferential anti-leukemic activity. Meta-iodobenzylguanidine however, partially reversed glucocorticoid resistance in 19% of the lymphoblastic leukemia samples.
Haarman
E G
EG
Department of Pediatric Hematology/Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. eg.haarman@vumc.nl
Kaspers
G J L
GJ
Pieters
R
R
Rottier
M M A
MM
Veerman
A J P
AJ
D049109:Cell Proliferation; D002648:Child; D003907:Dexamethasone / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008775:Methylprednisolone / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D011239:Prednisolone / Q000627:therapeutic use; D011281:Pregnatrienes / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D011281:Pregnatrienes; D003907:Dexamethasone; D011239:Prednisolone; D008775:Methylprednisolone; C005924:cortivazol