Circumvention of glucocorticoid resistance in childhood leukemia

Abstract 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...

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Bibliographic Details
Published in:Leukemia research 2008-09, Vol.32 (9), p.1417-1423
Main Authors: Haarman, E.G, Kaspers, G.J.L, Pieters, R, Rottier, M.M.A, Veerman, A.J.P
Format: Article
Language:English
Subjects:
Cell Proliferation
Child
Childhood leukemia
Cortivazol
Dexamethasone - therapeutic use
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
Glucocorticoid resistance
Glucocorticoids - therapeutic use
Hematology, Oncology and Palliative Medicine
Humans
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - pathology
Meta-iodobenzylguanidine
Methylprednisolone - therapeutic use
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology
Prednisolone - therapeutic use
Pregnatrienes - therapeutic use
Tumor Cells, Cultured
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Summary:Abstract 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.
ISSN:0145-2126
1873-5835
DOI:10.1016/j.leukres.2008.02.009