Hedgehog signaling is dispensable for adult murine hematopoietic stem cell function and hematopoiesis. Export

@article{citeulike:4845469, abstract = {We report the unexpected finding that loss of Hh signaling through conditional deletion of Smoothened (Smo) in the adult hematopoietic compartment has no apparent effect on adult hematopoiesis, including peripheral blood count, number or cell-cycle status of stem or progenitor cells, hematopoietic colony-forming potential, long-term repopulating activity in competitive repopulation assays, or stress response to serial 5-fluorouracil treatment. Furthermore, pharmacologic inhibition of Hh signaling with a potent and selective small molecule antagonist has no substantive effect on hematopoiesis in the mouse. In addition, Hh signaling is not required for the development of MLL-AF9-mediated acute myeloid leukemia (AML). Taken together, these data demonstrate that Hh signaling is dispensable for normal hematopoietic development and hematopoietic stem cell function, indicating that targeting of Hh signaling in solid tumors is not likely to result in hematopoietic toxicity. Furthermore, the Hh pathway may not be a compelling target in certain hematopoietic malignancies.}, author = {Hofmann, I. and Stover, E. H. and Cullen, D. E. and Mao, J. and Morgan, K. J. and Lee, B. H. and Kharas, M. G. and Miller, P. G. and Cornejo, M. G. and Okabe, R. and Armstrong, S. A. and Ghilardi, N. and Gould, S. and de Sauvage, F. J. and McMahon, A. P. and Gilliland, D. G.}, citeulike-article-id = {4845469}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.stem.2009.03.016}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19497284}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19497284}, doi = {10.1016/j.stem.2009.03.016}, issn = {1875-9777}, journal = {Cell stem cell}, keywords = {genetics, medicine, stem}, month = {June}, number = {6}, pages = {559--567}, posted-at = {2009-06-14 14:30:58}, priority = {2}, title = {Hedgehog signaling is dispensable for adult murine hematopoietic stem cell function and hematopoiesis.}, url = {http://dx.doi.org/10.1016/j.stem.2009.03.016}, volume = {4}, year = {2009} }

TY - JOUR ID - citeulike:4845469 L3 - citeulike-article-id:4845469 N2 - We report the unexpected finding that loss of Hh signaling through conditional deletion of Smoothened (Smo) in the adult hematopoietic compartment has no apparent effect on adult hematopoiesis, including peripheral blood count, number or cell-cycle status of stem or progenitor cells, hematopoietic colony-forming potential, long-term repopulating activity in competitive repopulation assays, or stress response to serial 5-fluorouracil treatment. Furthermore, pharmacologic inhibition of Hh signaling with a potent and selective small molecule antagonist has no substantive effect on hematopoiesis in the mouse. In addition, Hh signaling is not required for the development of MLL-AF9-mediated acute myeloid leukemia (AML). Taken together, these data demonstrate that Hh signaling is dispensable for normal hematopoietic development and hematopoietic stem cell function, indicating that targeting of Hh signaling in solid tumors is not likely to result in hematopoietic toxicity. Furthermore, the Hh pathway may not be a compelling target in certain hematopoietic malignancies. IS - 6 JF - Cell stem cell SN - 1875-9777 EP - 567 TI - Hedgehog signaling is dispensable for adult murine hematopoietic stem cell function and hematopoiesis. VL - 4 SP - 559 KW - genetics KW - medicine KW - stem AU - Hofmann, I AU - Stover, EH AU - Cullen, DE AU - Mao, J AU - Morgan, KJ AU - Lee, BH AU - Kharas, MG AU - Miller, PG AU - Cornejo, MG AU - Okabe, R AU - Armstrong, SA AU - Ghilardi, N AU - Gould, S AU - de Sauvage, FJ AU - McMahon, AP AU - Gilliland, DG PY - 2009/06/05/ UR - http://dx.doi.org/10.1016/j.stem.2009.03.016 ER -