Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells. Export

@article{citeulike:2938391, abstract = {Oncogenic tyrosine kinases, such as BCR-ABL, TEL-ABL, TEL-PDGFbetaR and FLT3-ITD, play a major role in the development of hematopoietic malignancy. They activate many of the same signal transduction pathways. To identify the critical target genes required for transformation in hematopoietic cells, we used a comparative gene expression strategy in which selective small molecules were applied to 32Dc13 cells that had been transformed to factor-independent growth by these respective oncogenic alleles. We identified inhibitor of DNA binding 1 (Id1), a gene involved in development, cell cycle and tumorigenesis, as a common target of these oncogenic kinases. These findings were prospectively confirmed in cell lines and primary bone marrow cells engineered to express the respective tyrosine kinase alleles, and were also confirmed in vivo in murine models of disease. Moreover, human AML cells lines Molm-14 and K562 that express the FLT3-ITD or BCR-ABL tyrosine kinases respectively, showed high levels of Id1 expression. Antisense and siRNA based knock-down of Id1 inhibited growth of these cells associated with increased p27(Kip1) expression and increased sensitivity to Trail-induced apoptosis. These findings indicate that Id1 is an important target of constitutively activated tyrosine kinases, and may be a therapeutic target for leukemias associated with oncogenic tyrosine kinases.}, address = {Hematology Division, Brigham and Women's Hospital, Boston, MA, United States.}, author = {Tam, Winnie F F. and Gu, Ting-Lei L. and Chen, Jing and Lee, Benjamin H H. and Bullinger, Lars and Frohling, Stefan and Wang, Andrew and Monti, Stefano and Golub, Todd R R. and Gilliland, D Gary G.}, citeulike-article-id = {2938391}, citeulike-linkout-0 = {http://dx.doi.org/10.1182/blood-2007-07-103010}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18559972}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18559972}, day = {17}, doi = {10.1182/blood-2007-07-103010}, issn = {1528-0020}, journal = {Blood}, keywords = {genetics, medicine, mesophysics}, month = {June}, posted-at = {2008-06-27 23:42:14}, priority = {2}, title = {Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells.}, url = {http://dx.doi.org/10.1182/blood-2007-07-103010}, year = {2008} }

TY - JOUR ID - citeulike:2938391 L3 - citeulike-article-id:2938391 N2 - Oncogenic tyrosine kinases, such as BCR-ABL, TEL-ABL, TEL-PDGFbetaR and FLT3-ITD, play a major role in the development of hematopoietic malignancy. They activate many of the same signal transduction pathways. To identify the critical target genes required for transformation in hematopoietic cells, we used a comparative gene expression strategy in which selective small molecules were applied to 32Dc13 cells that had been transformed to factor-independent growth by these respective oncogenic alleles. We identified inhibitor of DNA binding 1 (Id1), a gene involved in development, cell cycle and tumorigenesis, as a common target of these oncogenic kinases. These findings were prospectively confirmed in cell lines and primary bone marrow cells engineered to express the respective tyrosine kinase alleles, and were also confirmed in vivo in murine models of disease. Moreover, human AML cells lines Molm-14 and K562 that express the FLT3-ITD or BCR-ABL tyrosine kinases respectively, showed high levels of Id1 expression. Antisense and siRNA based knock-down of Id1 inhibited growth of these cells associated with increased p27(Kip1) expression and increased sensitivity to Trail-induced apoptosis. These findings indicate that Id1 is an important target of constitutively activated tyrosine kinases, and may be a therapeutic target for leukemias associated with oncogenic tyrosine kinases. JF - Blood SN - 1528-0020 AD - Hematology Division, Brigham and Women's Hospital, Boston, MA, United States. TI - Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells. KW - genetics KW - medicine KW - mesophysics AU - Tam, Winnie F AU - Gu, Ting-Lei AU - Chen, Jing AU - Lee, Benjamin H AU - Bullinger, Lars AU - Frohling, Stefan AU - Wang, Andrew AU - Monti, Stefano AU - Golub, Todd R AU - Gilliland, D Gary PY - 2008/06/17/ UR - http://dx.doi.org/10.1182/blood-2007-07-103010 ER -