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Blood, 1 June 2005, Vol. 105, No. 11, pp. 4477-4483. Prepublished online as a Blood First Edition Paper on February 10, 2005; DOI 10.1182/blood-2004-09-3706. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-09-3706v1 105/11/4477    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 Hammerman, P. S. Articles by Thompson, C. B. Search for Related Content PubMed PubMed Citation Articles by Hammerman, P. S. Articles by Thompson, C. B. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Pim and Akt oncogenes are independent regulators of hematopoietic cell growth and survival Peter S. Hammerman, Casey J. Fox, Morris J. Birnbaum, and Craig B. Thompson From the Department of Cancer Biology and Abramson Family Cancer Research Institute and the Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia. The Akt kinases promote hematopoietic cell growth and accumulation through phosphorylation of apoptotic effectors and stimulation of mTOR-dependent translation. In Akt-transformed leukemic cells, tumor growth can be inhibited by the mTOR inhibitor rapamycin, and clinical trials of rapamycin analogs for the treatment of leukemia are under way. Surprisingly, nontransformed hematopoietic cells can grow and proliferate in the presence of rapamycin. Here, we show that Pim-2 is required to confer rapamycin resistance. Primary hematopoietic cells from Pim-2– and Pim-1/Pim-2–deficient animals failed to accumulate and underwent apoptosis in the presence of rapamycin. Although animals deficient in Akt-1 or Pim-1/Pim-2 are viable, few animals with a compound deletion survived development, and those that were born had severe anemia. Primary hematopoietic cells from Akt-1/Pim-1/Pim-2–deficient animals displayed marked impairments in cell growth and survival. Conversely, ectopic expression of either Pim-2 or Akt-1 induced increased cell size and apoptotic resistance. However, though the effects of ectopic Akt-1 were reversed by rapamycin or a nonphosphorylatable form of 4EBP-1, those of Pim-2 were not. Coexpression of the transgenes in mice led to additive increases in cell size and survival and predisposed animals to rapid tumor formation. Together, these data indicate that Pim-2 and Akt-1 are critical components of overlapping but independent pathways, either of which is sufficient to promote the growth and survival of nontransformed hematopoietic cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A Pim kinase inhibitor, please Francis Giles Blood 2005 105: 4158-4159. [Full Text] [PDF] This article has been cited by other articles: K. M. Fischer, C. T. Cottage, W. Wu, S. Din, N. A. Gude, D. Avitabile, P. Quijada, B. L. Collins, J. Fransioli, and M. A. Sussman Enhancement of Myocardial Regeneration Through Genetic Engineering of Cardiac Progenitor Cells Expressing Pim-1 Kinase Circulation, November 24, 2009; 120(21): 2077 - 2087. [Abstract] [Full Text] [PDF] L. S. Chen, S. Redkar, D. Bearss, W. G. 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