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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4268-4275. Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2003-07-2193. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: 2003-07-2193v1 103/11/4268    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 Kharas, M. G Articles by Fruman, D. A Search for Related Content PubMed PubMed Citation Articles by Kharas, M. G Articles by Fruman, D. A Social Bookmarking                   What's this? Submitted July 1, 2003 Accepted January 29, 2004 Phosphoinositide 3-kinase signaling is essential for ABL oncogene mediated transformation of B lineage cells Michael G Kharas, Jonathan A Deane, Stephane Wong, Karen R O'Bosky, Naomi Rosenberg, Owen N Witte, and David A Fruman* Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA Pathology, Tufts University School of Medicine, Boston, MA, USA * Corresponding author; email: dfruman{at}uci.edi. v-ABL and BCR-ABL are oncogenic forms of the Abl tyrosine kinase that can cause leukemias in mice and humans. ABL oncogenes trigger multiple signaling pathways whose contribution to transformation varies among cell types. Activation of phosphoinositide 3-kinase (PI3K) is essential for ABL-dependent proliferation and survival in some cell types, and global PI3K inhibitors can enhance the anti-leukemia effects of the Abl kinase inhibitor imatinib. Although a significant fraction of BCR-ABL-induced human leukemias are of B cell origin, little is known about PI3K signaling mechanisms in B lineage cells transformed by ABL oncogenes. Here we show that activation of class IA PI3K and downstream inactivation of FOXO transcription factors is essential for survival of murine pro/pre-B cells transformed by v-ABL or BCR-ABL. In addition, analysis of mice lacking individual PI3K genes indicates that products of the Pik3r1 gene contribute to transformation efficiency by BCR-ABL. These findings establish a role for PI3K signaling in B lineage transformation by ABL oncogenes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Yusuf, M. G. Kharas, J. Chen, R. Q. Peralta, A. Maruniak, P. Sareen, V. W. Yang, K. H. Kaestner, and D. A. Fruman KLF4 is a FOXO target gene that suppresses B cell proliferation Int. Immunol., May 1, 2008; 20(5): 671 - 681. [Abstract] [Full Text] [PDF] K. U. Birkenkamp, A. Essafi, K. E. van der Vos, M. da Costa, R. C.-Y. Hui, F. Holstege, L. Koenderman, E. W.-F. Lam, and P. J. Coffer FOXO3a Induces Differentiation of Bcr-Abl-transformed Cells through Transcriptional Down-regulation of Id1 J. Biol. Chem., January 26, 2007; 282(4): 2211 - 2220. [Abstract] [Full Text] [PDF] M. G. Kharas, I. Yusuf, V. M. Scarfone, V. W. Yang, J. A. Segre, C. S. Huettner, and D. A. Fruman KLF4 suppresses transformation of pre-B cells by ABL oncogenes Blood, January 15, 2007; 109(2): 747 - 755. [Abstract] [Full Text] [PDF] J. Chen, I. Yusuf, H.-M. Andersen, and D. A. Fruman FOXO Transcription Factors Cooperate with {delta}EF1 to Activate Growth Suppressive Genes in B Lymphocytes. J. Immunol., March 1, 2006; 176(5): 2711 - 2721. [Abstract] [Full Text] [PDF] R. Cruz, L. Hedden, D. Boyer, M. G. Kharas, D. A. Fruman, and K. K. Lee-Fruman S6 kinase 2 potentiates interleukin-3-driven cell proliferation J. Leukoc. Biol., December 1, 2005; 78(6): 1378 - 1385. [Abstract] [Full Text] [PDF] S.-y. Ren, E. Bolton, M. G. Mohi, A. Morrione, B. G. Neel, and T. Skorski Phosphatidylinositol 3-Kinase p85{alpha} Subunit-Dependent Interaction with BCR/ABL-Related Fusion Tyrosine Kinases: Molecular Mechanisms and Biological Consequences Mol. Cell. Biol., September 15, 2005; 25(18): 8001 - 8008. [Abstract] [Full Text] [PDF] P.-H. Tseng, H.-P. Lin, J. Zhu, K.-F. Chen, E. M. Hade, D. C. Young, J. C. Byrd, M. Grever, K. Johnson, B. J. Druker, et al. Synergistic interactions between imatinib mesylate and the novel phosphoinositide-dependent kinase-1 inhibitor OSU-03012 in overcoming imatinib mesylate resistance Blood, May 15, 2005; 105(10): 4021 - 4027. [Abstract] [Full Text] [PDF] M. G. Kharas and D. A. Fruman ABL Oncogenes and Phosphoinositide 3-Kinase: Mechanism of Activation and Downstream Effectors Cancer Res., March 15, 2005; 65(6): 2047 - 2053. [Abstract] [Full Text] [PDF] S. Wong, J. McLaughlin, D. Cheng, C. Zhang, K. M. Shokat, and O. N. Witte Sole BCR-ABL inhibition is insufficient to eliminate all myeloproliferative disorder cell populations PNAS, December 14, 2004; 101(50): 17456 - 17461. [Abstract] [Full Text] [PDF]

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