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Related Collections Plenary Papers Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 January 2001, Vol. 97, No. 1, pp. 4-13 PLENARY PAPER The Src homology 2 domain of Bcr/Abl is required for efficient induction of chronic myeloid leukemia-like disease in mice but not for lymphoid leukemogenesis or activation of phosphatidylinositol 3-kinase Sergei Roumiantsev, Isabel E. de Aos, Lyuba Varticovski, Robert L. Ilaria, and Richard A. Van Etten From the Center for Blood Research, Department of Genetics, Harvard Medical School, Boston, MA; Department of Biomedical Research, St Elizabeth's Hospital, Tufts University School of Medicine, Boston, MA; and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX. The effect of mutations in the Src homology 2 (SH2) domain of the BCR/ABL oncogene on leukemogenesis was tested in a quantitative murine bone marrow transduction/transplantation assay that accurately models human Philadelphia-positive B-lymphoid leukemia and chronic myeloid leukemia (CML). The SH2 domain was not required for induction of B-lymphoid leukemia in mice by BCR/ABL. Under conditions where the p190 and p210 forms of BCR/ABL induce fatal CML-like myeloproliferative disease within 4 weeks, p210 SH2 mutants induced CML-like disease in some mice only after a significant delay, with other recipients succumbing to B-lymphoid leukemia instead. In contrast, p190 BCR/ABL SH2 point and deletion mutants rapidly induced CML-like disease. These results provide the first direct evidence of significant differences in cell signaling by the Bcr/Abl tyrosine kinase between these distinct leukemias. Contrary to previous observations, high levels of phosphatidylinositol 3-kinase (PI 3-kinase) activity in primary malignant lymphoblasts and myeloid cells from recipients of marrow transduced with the BCR/ABL SH2 mutants were found. Hence, the decreased induction of CML-like disease by the p210 BCR/ABL SH2 mutants is not due to impaired activation of PI 3-kinase. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Acquaviva, X. Chen, and R. Ren IRF-4 functions as a tumor suppressor in early B-cell development Blood, November 1, 2008; 112(9): 3798 - 3806. [Abstract] [Full Text] [PDF] J. Ko, N. Patel, T. Ikawa, H. Kawamoto, O. Frank, R. R. Rivera, R. A. Van Etten, and C. Murre Suppression of E-protein activity interferes with the development of BCR-ABL-mediated myeloproliferative disease PNAS, September 2, 2008; 105(35): 12967 - 12972. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020