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Gefitinib induces myeloid differentiation of acute myeloid leukemia
| Content Provider | Scilit |
|---|---|
| Author | Stegmaier, Kimberly Corsello, Steven M. Ross, Kenneth N. Wong, Jenny S. DeAngelo, Daniel J. Golub, Todd R. |
| Copyright Year | 2005 |
| Description | 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. (Blood. 2005;106: 2841-2848) |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895296/pdf |
| Ending Page | 2848 |
| Page Count | 8 |
| Starting Page | 2841 |
| DOI | 10.1182/blood-2005-02-0488 |
| Journal | Blood |
| Issue Number | 8 |
| Volume Number | 106 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2005-10-15 |
| Access Restriction | Open |
| Subject Keyword | Hematology Research and Experimental Medicine Acute Myeloid Leukemia Aml Gene Expression Neutrophilic Egfr Gefitinib Induces Fda Differentiation Journal: Blood (Vol- 104, Issue- 8) |
| Content Type | Text |
| Resource Type | Article |
