SEARCH:   Advanced

Blood, 15 March 2005, Vol. 105, No. 6, pp. 2527-2534. Prepublished online as a Blood First Edition Paper on November 18, 2004; DOI 10.1182/blood-2004-06-2494. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-06-2494v1 105/6/2527    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 Récher, C. Articles by Payrastre, B. Search for Related Content PubMed PubMed Citation Articles by Récher, C. Articles by Payrastre, B. Related Collections Neoplasia Signal Transduction Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Antileukemic activity of rapamycin in acute myeloid leukemia Christian Récher, Odile Beyne-Rauzy, Cécile Demur, Gaëtan Chicanne, Cédric Dos Santos, Véronique Mansat-De Mas, David Benzaquen, Guy Laurent, Françoise Huguet, and Bernard Payrastre From Institut National de la Santé et de la Recherche Médicale (Inserm) U563, CPTP, Département d'Oncogenèse et signalisation dans les cellules hématopoïétiques, IFR30, Toulouse, France; the Service d'Hématologie, Centre Hospitalier Universitaire Purpan, Toulouse, France; the Laboratoire d'Hématologie, Centre Hospitalier Universitaire Purpan, Toulouse, France; and the Service d'Orthopédie, Centre Hospitalier Universitaire Purpan, Toulouse, France. The mammalian target of rapamycin (mTOR) is a key regulator of growth and survival in many cell types. Its constitutive activation has been involved in the pathogenesis of various cancers. In this study, we show that mTOR inhibition by rapamycin strongly inhibits the growth of the most immature acute myeloid leukemia (AML) cell lines through blockade in G0/G1 phase of the cell cycle. Accordingly, 2 downstream effectors of mTOR, 4E-BP1 and p70S6K, are phosphorylated in a rapamycin-sensitive manner in a series of 23 AML cases. Interestingly, the mTOR inhibitor markedly impairs the clonogenic properties of fresh AML cells while sparing normal hematopoietic progenitors. Moreover, rapamycin induces significant clinical responses in 4 of 9 patients with either refractory/relapsed de novo AML or secondary AML. Overall, our data strongly suggest that mTOR is aberrantly regulated in most AML cells and that rapamycin and analogs, by targeting the clonogenic compartment of the leukemic clone, may be used as new compounds in AML therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. A. Rizzieri, E. Feldman, J. F. DiPersio, N. Gabrail, W. Stock, R. Strair, V. M. Rivera, M. Albitar, C. L. Bedrosian, and F. J. Giles A Phase 2 Clinical Trial of Deforolimus (AP23573, MK-8669), a Novel Mammalian Target of Rapamycin Inhibitor, in Patients with Relapsed or Refractory Hematologic Malignancies Clin. Cancer Res., May 1, 2008; 14(9): 2756 - 2762. [Abstract] [Full Text] [PDF] E. Weisberg, L. Banerji, R. D. Wright, R. Barrett, A. Ray, D. Moreno, L. Catley, J. Jiang, E. Hall-Meyers, M. Sauveur-Michel, et al. Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells Blood, April 1, 2008; 111(7): 3723 - 3734. [Abstract] [Full Text] [PDF] C. Dos Santos, C. Demur, V. Bardet, N. Prade-Houdellier, B. Payrastre, and C. Recher A critical role for Lyn in acute myeloid leukemia Blood, February 15, 2008; 111(4): 2269 - 2279. [Abstract] [Full Text] [PDF] E. E.W. Cohen mTOR: The Mammalian Target of Replication J. Clin. Oncol., January 20, 2008; 26(3): 348 - 349. [Full Text] [PDF] J. Tamburini, N. Chapuis, V. Bardet, S. Park, P. Sujobert, L. Willems, N. Ifrah, F. Dreyfus, P. Mayeux, C. Lacombe, et al. Mammalian target of rapamycin (mTOR) inhibition activates phosphatidylinositol 3-kinase/Akt by up-regulating insulin-like growth factor-1 receptor signaling in acute myeloid leukemia: rationale for therapeutic inhibition of both pathways Blood, January 1, 2008; 111(1): 379 - 382. [Abstract] [Full Text] [PDF] K. W.L. Yee, Z. Zeng, M. Konopleva, S. Verstovsek, F. Ravandi, A. Ferrajoli, D. Thomas, W. Wierda, E. Apostolidou, M. Albitar, et al. Phase I/II Study of the Mammalian Target of Rapamycin Inhibitor Everolimus (RAD001) in Patients with Relapsed or Refractory Hematologic Malignancies Clin. Cancer Res., September 1, 2006; 12(17): 5165 - 5173. [Abstract] [Full Text] [PDF] N. Boissel, D. Rea, V. Tieng, N. Dulphy, M. Brun, J.-M. Cayuela, P. Rousselot, R. Tamouza, P. Le Bouteiller, F.-X. Mahon, et al. BCR/ABL oncogene directly controls MHC class I chain-related molecule A expression in chronic myelogenous leukemia. J. Immunol., April 15, 2006; 176(8): 5108 - 5116. [Abstract] [Full Text] [PDF] A. L. Drayer, S. G. M. Olthof, and E. Vellenga Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors Stem Cells, January 1, 2006; 24(1): 105 - 114. [Abstract] [Full Text] [PDF] Q. Xu, J. E. Thompson, and M. Carroll mTOR regulates cell survival after etoposide treatment in primary AML cells Blood, December 15, 2005; 106(13): 4261 - 4268. [Abstract] [Full Text] [PDF]

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