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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2841-2848. Prepublished online as a Blood First Edition Paper on July 5, 2005; DOI 10.1182/blood-2005-02-0488. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 2005-02-0488v1 106/8/2841    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Stegmaier, K. Articles by Golub, T. R. Search for Related Content PubMed PubMed Citation Articles by Stegmaier, K. Articles by Golub, T. R. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Gefitinib induces myeloid differentiation of acute myeloid leukemia Kimberly Stegmaier, Steven M. Corsello, Kenneth N. Ross, Jenny S. Wong, Daniel J. DeAngelo, and Todd R. Golub From the Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital Boston, Harvard Medical School, Boston, MA; The Eli and Edythe L. Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, MA; Howard Hughes Medical Institute, Chevy Chase, MD; and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA. 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) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Gefitinib adopts orphan kinases in leukemia Animesh Pardanani and Ayalew Tefferi Blood 2005 106: 2600-2601. [Full Text] [PDF] This article has been cited by other articles: V. Pitini, C. Arrigo, and G. Altavilla Erlotinib in a Patient With Acute Myelogenous Leukemia and Concomitant Non-Small-Cell Lung Cancer J. Clin. Oncol., July 20, 2008; 26(21): 3645 - 3646. [Full Text] [PDF] S. Boehrer, L. Ades, T. Braun, L. Galluzzi, J. Grosjean, C. Fabre, G. Le Roux, C. Gardin, A. Martin, S. de Botton, et al. Erlotinib exhibits antineoplastic off-target effects in AML and MDS: a preclinical study Blood, February 15, 2008; 111(4): 2170 - 2180. [Abstract] [Full Text] [PDF] G. Chan and M. Pilichowska Complete remission in a patient with acute myelogenous leukemia treated with erlotinib for non small-cell lung cancer Blood, August 1, 2007; 110(3): 1079 - 1080. [Full Text] [PDF]

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