Transcription profiling of human pretreatment glucocortocoid sensitive and resistant primary leukaemias

ABSTRACT: Drug resistance remains a major obstacle to successful cancer treatment. Here we use a novel approach to identify rapamycin as a glucocorticoid resistance reversal agent. A database of drug-associated gene expression profiles was screened for molecules whose profile overlapped with a gene expression signature of glucocorticoid (GC) sensitivity/resistance in Acute Lymphoblastic Leukemia (ALL) cells. The screen indicated the mTOR inhibitor rapamycin profile matched the signature of GC-sensitivity. We thus tested the hypothesis that rapamycin would induce GC sensitivity in lymphoid malignancy cells, and found that it sensitized cells to glucocorticoid induced apoptosis via modulation of antiapoptotic MCL1. These data indicate that MCL1 is an important regulator of GC-induced apoptosis, and th

ORGANISM(S): Homo sapiens

SUBMITTER: Scott Armstrong 

PROVIDER: E-GEOD-5820 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress