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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1677-1685. Prepublished online as a Blood First Edition Paper on November 27, 2007; DOI 10.1182/blood-2007-04-083808. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-04-083808v1 111/3/1677    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 Chen, J.-L. Articles by Rothman, P. B. Search for Related Content PubMed PubMed Citation Articles by Chen, J.-L. Articles by Rothman, P. B. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Pim-1 and Pim-2 kinases are required for efficient pre–B-cell transformation by v-Abl oncogene Ji-Long Chen1, Andre Limnander1, and Paul B. Rothman1 1 Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City The precise mechanisms by which Abl oncogenes transform hematopoietic cells are unknown. We have examined the role of Pim kinases in v-Abl–mediated transformation. In v-Abl transformants, expression of Pim-1 and Pim-2, but not Pim-3, is dependent on Abl kinase activity. Transformation assays demonstrate that v-Abl cannot efficiently transform bone marrow cells derived from Pim-1–/–/Pim-2–/– mice. Ectopic expression of either Pim-1 or Pim-2 in Pim-1–/–/Pim-2–/– cells restores transformation by v-Abl, strongly suggesting that either Pim-1 or Pim-2 is required for v-Abl–mediated tumorigenesis. Interestingly, the combined deficiency of Pim-1, Pim-2, and Suppressor of Cytokine Signalling (SOCS)-1 resulted in partial restoration of v-Abl transformation efficiency. In addition, Pim kinases are involved in modification of SOCS-1 and in regulating SOCS-1 protein levels in v-Abl–transformed cells. Furthermore, Pim kinases regulate the proapoptotic proteins Bcl-XS and BAD. Pim kinases inhibit the expression of Bcl-XS. Pim deficiency decreases the phosphorylation levels of BAD, whereas ectopic expression of Pim-1 increases the amount of phospho-BAD. This correlates with an increased protection from apoptosis in Abl transformants expressing Pim kinases. Together, these data suggest that Pim kinases play a key role in the v-Abl transformation, possibly via participating in modulation of SOCS-1 and via regulating the apoptotic signaling. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. S. Chen, S. Redkar, D. Bearss, W. G. Wierda, and V. Gandhi Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells Blood, November 5, 2009; 114(19): 4150 - 4157. [Abstract] [Full Text] [PDF] J. Tamburini, A. S. Green, V. Bardet, N. Chapuis, S. Park, L. Willems, M. Uzunov, N. Ifrah, F. Dreyfus, C. Lacombe, et al. Protein synthesis is resistant to rapamycin and constitutes a promising therapeutic target in acute myeloid leukemia Blood, August 20, 2009; 114(8): 1618 - 1627. [Abstract] [Full Text] [PDF] J. Elliott, Y. Suessmuth, L. M. Scott, K. Nahlik, M. F. McMullin, S. N. Constantinescu, A. R. Green, and J. A. Johnston SOCS3 tyrosine phosphorylation as a potential bio-marker for myeloproliferative neoplasms associated with mutant JAK2 kinases Haematologica, April 1, 2009; 94(4): 576 - 580. [Abstract] [Full Text] [PDF]

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