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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2452-2461. Prepublished online as a Blood First Edition Paper on June 21, 2005; DOI 10.1182/blood-2005-02-0734. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-02-0734v1 106/7/2452    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 Luo, H. Articles by Tomasson, M. H Search for Related Content PubMed PubMed Citation Articles by Luo, H. Articles by Tomasson, M. H Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 23, 2005 Accepted May 16, 2005 c-Myc rapidly induces acute myeloid leukemia in mice without evidence of lymphoma-associated anti-apoptotic mutations Hui Luo, Qing Li, Julie O'Neal, Friederike Kreisel, Michelle M Le Beau, and Michael H Tomasson* Department of Medicine and Genetics, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA Department of Pathology, Washington University School of Medicine, St. Louis, MO, USA Department of Hematology/Oncology, University of Chicago, Chicago, IL, USA * Corresponding author; email: tomasson{at}wustl.edu. Ectopic expression of c-Myc (Myc) in most primary cell types results in programmed cell death, and malignant transformation cannot occur without additional mutations that block apoptosis. The development of Myc-induced lymphoid tumors has been well studied and supports this model. Myc can be upregulated in acute myeloid leukemia (AML), but its exact role in myeloid leukemogenesis is unclear. To study its role in AML, we utilized a Murine Stem Cell Virus (MSCV) retroviral gene trans-fer/transplantation system to broadly express Myc in the bone marrow of mice either alone or in combination with anti-apoptotic mutations. Myc expression, either in the context of Arf/Ink4a loss, or Bcl-2 co-expression, induced a mixture of acute myeloid and acute lymphoid leukemias (AML+ALL). In the absence of anti-apoptotic mutations however, all MSCV-Myc transplanted mice (100%, N=110) devel-oped AML exclusively. MSCV-Myc-induced AML was polyclonal, readily transplantable, possessed an intact Arf-p53 pathway, and did not display cytogenetic abnormalities by spectral karyotyping (SKY) analysis. Lastly, we found that Myc preferentially stimulated the growth of myeloid progenitor cells in methylcellulose. These data provide the first direct evidence that Myc is a critical downstream effector of myeloid leukemogenesis and suggest that myeloid progenitors are intrinsically resistant to Myc-induced apoptosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Guo, C. Niu, P. Breslin, M. Tang, S. Zhang, W. Wei, A. R. Kini, G. P. Paner, S. Alkan, S. W. Morris, et al. c-Myc-mediated control of cell fate in megakaryocyte-erythrocyte progenitors Blood, September 3, 2009; 114(10): 2097 - 2106. [Abstract] [Full Text] [PDF] P. Bonetti, T. Davoli, C. Sironi, B. Amati, P. G. Pelicci, and E. Colombo Nucleophosmin and its AML-associated mutant regulate c-Myc turnover through Fbw7{gamma} J. Cell Biol., October 23, 2008; 182(1): 19 - 26. [Abstract] [Full Text] [PDF] M. Wall, G. Poortinga, K. M. Hannan, R. B. Pearson, R. D. Hannan, and G. A. McArthur Translational control of c-MYC by rapamycin promotes terminal myeloid differentiation Blood, September 15, 2008; 112(6): 2305 - 2317. [Abstract] [Full Text] [PDF] H. Kawagoe, A. Kandilci, T. A. Kranenburg, and G. C. Grosveld Overexpression of N-Myc Rapidly Causes Acute Myeloid Leukemia in Mice Cancer Res., November 15, 2007; 67(22): 10677 - 10685. [Abstract] [Full Text] [PDF] C. Parikh, R. Subrahmanyam, and R. Ren Oncogenic NRAS, KRAS, and HRAS Exhibit Different Leukemogenic Potentials in Mice Cancer Res., August 1, 2007; 67(15): 7139 - 7146. [Abstract] [Full Text] [PDF] A. Boyapati, M. Yan, L. F. Peterson, J. R. Biggs, M. M. Le Beau, and D.-E. Zhang A leukemia fusion protein attenuates the spindle checkpoint and promotes aneuploidy Blood, May 1, 2007; 109(9): 3963 - 3971. [Abstract] [Full Text] [PDF] J. A. Cain, Z. Xiang, J. O'Neal, F. Kreisel, A. Colson, H. Luo, L. Hennighausen, and M. H. Tomasson Myeloproliferative disease induced by TEL-PDGFRB displays dynamic range sensitivity to Stat5 gene dosage Blood, May 1, 2007; 109(9): 3906 - 3914. [Abstract] [Full Text] [PDF] Z. Xiang, F. Kreisel, J. Cain, A. Colson, and M. H. Tomasson Neoplasia Driven by Mutant c-KIT Is Mediated by Intracellular, Not Plasma Membrane, Receptor Signaling Mol. Cell. Biol., January 1, 2007; 27(1): 267 - 282. [Abstract] [Full Text] [PDF]

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