Receptor mutation is not a common mechanism of naturally occurring glucocorticoid resistance in leukaemia cell lines.
Glucocorticoids (GCs) are among the most important drugs for the treatment of acute lymphoblastic leukaemia (ALL). Cell lines cultured in high GC concentrations typically contain mutated glucocorticoid receptor (GR), something that is rarely found in primary ALL specimens. We studied naturally occurring mechanisms of GC resistance and examined sensitivity to GC in 15 T-ALL cell lines grown without prior exposure to drugs. Resistance could not be attributed to mutations in GR or variations in levels of its expression. We conclude that this panel of cell lines provides a suitable in vitro model since it reflects GC resistance in primary ALL.
Beesley
Alex H
AH
Division of Children's Leukaemia and Cancer Research, Telethon Institute for Child Health Research, University of Western Australia Centre for Child Health Research, Perth, Australia.
Weller
Renae E
RE
Senanayake
Saranga
S
Welch
Mathew
M
Kees
Ursula R
UR
D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008775:Methylprednisolone / Q000494:pharmacology; D009154:Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D011965:Receptors, Glucocorticoid / Q000235:genetics*
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D008775:Methylprednisolone