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Blood, 15 July 2006, Vol. 108, No. 2, pp. 653-661. Prepublished online as a Blood First Edition Paper on March 14, 2006; DOI 10.1182/blood-2006-01-0172. This Article Full Text Full Text (PDF) All Versions of this Article: 2006-01-0172v1 108/2/653    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 Smith, D. P. Articles by Cory, S. Search for Related Content PubMed PubMed Citation Articles by Smith, D. P. Articles by Cory, S. Related Collections Apoptosis Oncogenes and Tumor Suppressors Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA MYC levels govern hematopoietic tumor type and latency in transgenic mice Darrin P. Smith, Mary L. Bath, Donald Metcalf, Alan W. Harris, and Suzanne Cory From The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. Deregulated MYC expression has been implicated in the etiology of many human cancers, including hematopoietic malignancies. To explore the impact of widespread constitutive MYC expression in the hematopoietic compartment, we have used a vector containing regulatory elements of the Vav gene to generate transgenic mice. VavP-MYC mice are highly tumor-prone and the level of MYC was found to influence both the kinetics and nature of the malignancies that developed. Whereas aggressive T-cell lymphomas rapidly overwhelmed the highest-expressing line, late-onset monocytic tumors greatly predominated in 2 low-expressing lines. These monocytic tumors most likely arise from abnormal macrophage colony-stimulating factor (M-CSF)–dependent progenitor cells having enhanced self-generative capacity. There appears to be a sharp threshold for MYC-induced T-cell lymphomagenesis because merely doubling the MYC level in a low-expressing line by breeding homozygous transgenic animals switched the phenotype from primarily monocytic tumors to exclusively T-cell tumors. Even the low level of MYC, however, clearly affected T-cell cycling, size, and sensitivity to apoptosis, and coexpression of a BCL2 transgene promoted efficient T-cell lymphomagenesis. The implication is that MYC level affects the spontaneous acquisition of synergistic oncogenic mutations. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Distinct MYC thresholds in hematopoietic neoplasia Siegfried Janz Blood 2006 108: 413. [Full Text] [PDF] This article has been cited by other articles: M. Reimann, C. Loddenkemper, C. Rudolph, I. Schildhauer, B. Teichmann, H. Stein, B. Schlegelberger, B. Dorken, and C. A. Schmitt The Myc-evoked DNA damage response accounts for treatment resistance in primary lymphomas in vivo Blood, October 15, 2007; 110(8): 2996 - 3004. [Abstract] [Full Text] [PDF]

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