SEARCH:   Advanced

Blood, 1 February 2005, Vol. 105, No. 3, pp. 1222-1230. Prepublished online as a Blood First Edition Paper on October 12, 2004; DOI 10.1182/blood-2004-03-0802. This Article Full Text (PDF) All Versions of this Article: 2004-03-0802v1 105/3/1222    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 Wermuth, P. J Articles by Buchberg, A. M Search for Related Content PubMed PubMed Citation Articles by Wermuth, P. J Articles by Buchberg, A. M Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 4, 2004 Accepted September 11, 2004 Meis1-mediated apoptosis is caspase-dependent and can be suppressed by coexpression of HoxA9 in murine and human cell Lines Peter J Wermuth and Arthur M Buchberg* Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA * Corresponding author; email: buchberg{at}mail.jci.tju.edu. Coexpression of the homeodomain protein Meis1 and either HoxA7 or HoxA9 is characteristic of many acute myelogenous leukemias. Although Meis1 can be overexpressed in bone marrow long-term repopulating cells, it is incapable of mediating their transformation. While overexpressing HoxA9 alone transforms murine bone marrow cells, concurrent Meis1 overexpression greatly accelerates oncogenesis. Meis1-HoxA9 cooperation suppresses several myeloid differentiation pathways. We now report that Meis1 overexpression strongly induces apoptosis in a variety of cell types in vitro via a caspase-dependent process. Meis1 requires a functional homeodomain and Pbx-interaction motif to induce apoptosis. Coexpressing HoxA9 with Meis1suppresses this apoptosis and provides protection from several apoptosis inducers. Pbx1, another Meis1 cofactor, also induces apoptosis; however, coexpressing HoxA9 is incapable of rescuing Pbx-mediated apoptosis. This resistance to apoptotic stimuli, coupled with the previously reported ability to suppress multiple myeloid differentiation pathways, would provide a strong selective advantage to Meis1-HoxA9 coexpressing cells, in vivo, leading to leukemogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Meis and Hox: a mighty pair defeats apoptosis Takuro Nakamura Blood 2005 105: 909-910. [Full Text] [PDF] This article has been cited by other articles: 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] W. Fiskus, M. Pranpat, M. Balasis, B. Herger, R. Rao, A. Chinnaiyan, P. Atadja, and K. Bhalla Histone deacetylase inhibitors deplete enhancer of zeste 2 and associated polycomb repressive complex 2 proteins in human acute leukemia cells Mol. Cancer Ther., December 1, 2006; 5(12): 3096 - 3104. [Abstract] [Full Text] [PDF] M. Fischer, A. Oberthuer, B. Brors, Y. Kahlert, M. Skowron, H. Voth, P. Warnat, K. Ernestus, B. Hero, and F. Berthold Differential Expression of Neuronal Genes Defines Subtypes of Disseminated Neuroblastoma with Favorable and Unfavorable Outcome Clin. Cancer Res., September 1, 2006; 12(17): 5118 - 5128. [Abstract] [Full Text] [PDF] M. Thomas, A. Gessner, H.-P. Vornlocher, P. Hadwiger, J. Greil, and O. Heidenreich Targeting MLL-AF4 with short interfering RNAs inhibits clonogenicity and engraftment of t(4;11)-positive human leukemic cells Blood, November 15, 2005; 106(10): 3559 - 3566. [Abstract] [Full Text] [PDF] H. J. Lawrence and C. Largman The HOX-MEIS connection in AML Blood, July 1, 2005; 106(1): 6 - 7. [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020