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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4907-4913. Prepublished online as a Blood First Edition Paper on February 22, 2007; DOI 10.1182/blood-2006-10-051847. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2006-10-051847v1 109/11/4907    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 Kelly, P. N. Articles by Strasser, A. Search for Related Content PubMed PubMed Citation Articles by Kelly, P. N. Articles by Strasser, A. Related Collections Neoplasia Apoptosis Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Endogenous bcl-2 is not required for the development of Eµ-myc–induced B-cell lymphoma Priscilla N. Kelly1,2, Hamsa Puthalakath1, Jerry M. Adams1, and Andreas Strasser1 1 The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; 2 Department of Medical Biology, The University of Melbourne, Melbourne, Australia Although myc and bcl-2 synergize in tumor development, particularly lymphomagenesis, it is not known whether endogenous bcl-2 is required for myc-induced tumorigenesis. To investigate the role of endogenous Bcl-2 in myc-induced lymphomagenesis, we bypassed the early death of Bcl-2–deficient mice by reconstituting lethally irradiated wild-type (wt) mice with a hematopoietic system from fetal liver–derived stem cells of Eµ-myc/bcl-2–/– or control Eµ-myc transgenic embryos. In premalignant (healthy) recipients, loss of Bcl-2 caused a moderate decrease in pre-B and immature B cells, and a dramatic reduction of mature B lymphocytes expressing the Eµ-myc transgene. Furthermore, cultured preneoplastic Eµ-myc/bcl-2–/– mature B cells displayed accelerated apoptosis compared with Eµ-myc B cells. However, despite the striking reduction in B-cell numbers in vivo, ablation of endogenous Bcl-2 did not prevent or even delay development of Eµ-myc lymphoma. Moribund mice presented with similar degrees of splenomegaly, blood leukocyte numbers, and tumor dissemination at death. These findings demonstrate that the initiation, development, continued growth, and severity of Eµ-myc lymphoma do not depend upon endogenous Bcl-2, nor upon the total number of B lymphoid cells driven by the Eµ-myc transgene. These results have implications for the treatment of hematopoietic tumors, particularly those that are not caused by Bcl-2 overexpression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Newbold, R. K. Lindemann, L. A. Cluse, K. F. Whitecross, A. E. Dear, and R. W. Johnstone Characterisation of the novel apoptotic and therapeutic activities of the histone deacetylase inhibitor romidepsin Mol. Cancer Ther., May 1, 2008; 7(5): 1066 - 1079. [Abstract] [Full Text] [PDF] D. Hanahan, E. F. Wagner, and R. D. Palmiter The origins of oncomice: a history of the first transgenic mice genetically engineered to develop cancer Genes & Dev., September 15, 2007; 21(18): 2258 - 2270. [Abstract] [Full Text] [PDF]

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