SEARCH:   Advanced

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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 4, 2005 Accepted June 12, 2005 Gefitinib (Iressa) 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* Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital Boston, Harvard Medical School, Boston, MA, USA The Eli and Edythe L. Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital Boston, Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital Boston, Harvard Medical School, Boston, MA, USA; The Eli and Edythe L. Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA * Corresponding author; email: golub{at}broad.mit.edu. 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 4,5-dianilinophthalimide (DAPH1), previously reported to inhibit epidermal growth factor receptor (EGFR) kinase activity. Here, we report that the FDA-approved EGFR inhibitor gefitinib (Iressa) similarly promotes the differentiation of AML cell lines and primary patient-derived AML blasts in vitro. Gefitinib induced differentiation based on morphological 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. 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: R. M. Stone and D. J. DeAngelo Screens, iron, and leukemia Blood, October 1, 2009; 114(14): 2857 - 2858. [Full Text] [PDF] D. Nowak, D. Stewart, and H. P. Koeffler Differentiation therapy of leukemia: 3 decades of development Blood, April 16, 2009; 113(16): 3655 - 3665. [Abstract] [Full Text] [PDF] J. Faber, A. V. Krivtsov, M. C. Stubbs, R. Wright, T. N. Davis, M. van den Heuvel-Eibrink, C. M. Zwaan, A. L. Kung, and S. A. Armstrong HOXA9 is required for survival in human MLL-rearranged acute leukemias Blood, March 12, 2009; 113(11): 2375 - 2385. [Abstract] [Full Text] [PDF] K. Hotta, K. Kiura, N. Takigawa, K. Matsuo, M. Tabata, Y. Fujiwara, and M. Tanimoto Paradoxical Clinical Effects of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors for Acute Myelogenous Leukemia J. Clin. Oncol., December 10, 2008; 26(35): 5826 - 5827. [Full Text] [PDF] V. Pitini, C. Arrigo, and G. Altavilla In Reply J. Clin. Oncol., December 10, 2008; 26(35): 5827 - 5827. [Full Text] [PDF] 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]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020