Transcriptomics

Dataset Information

0

CaArray_golub-00392: Gefitinib (Iressa) induces myeloid differentiation of acute myeloid leukemia


ABSTRACT: Cure rates for patients with acute myeloid leukemia (AML) remain low despite ever-increasing dose intensity of cytotoxic therapy. In an effort to identify novel approaches to AML therapy, we recently reported a new method of chemical screening based on the modulation of a gene expression signature of interest. We applied this approach to the discovery of AML-differentiation-promoting compounds. Among the compounds inducing neutrophilic differentiation was DAPH1 (4,5-dianilinophthalimide), previously reported to inhibit epidermal growth factor receptor (EGFR) kinase activity. Here we report that the Food and Drug Administration (FDA)-approved EGFR inhibitor gefitinib similarly promotes the differentiation of AML cell lines and primary patient-derived AML blasts in vitro. Gefitinib induced differentiation based on morphologic assessment, nitro-blue tetrazolium reduction, cell-surface markers, genome-wide patterns of gene expression, and inhibition of proliferation at clinically achievable doses. Importantly, EGFR expression was not detected in AML cells, indicating that gefitinib functions through a previously unrecognized EGFR-independent mechanism. These studies indicate that clinical trials testing the efficacy of gefitinib in patients with AML are warranted.

ORGANISM(S): Homo sapiens

PROVIDER: GSE68954 | GEO | 2015/05/16

SECONDARY ACCESSION(S): PRJNA284159

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2015-05-16 | E-GEOD-68954 | biostudies-arrayexpress
2021-11-02 | PXD022038 | Pride
2024-06-03 | PXD050623 | Pride
2022-06-01 | GSE178787 | GEO
2019-04-24 | GSE113271 | GEO
2007-09-20 | E-GEOD-995 | biostudies-arrayexpress
2016-07-01 | E-GEOD-75307 | biostudies-arrayexpress
2016-07-01 | E-GEOD-75308 | biostudies-arrayexpress
2016-07-01 | GSE75307 | GEO
2016-07-01 | GSE75308 | GEO