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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4170-4177. Prepublished online as a Blood First Edition Paper on August 29, 2006; DOI 10.1182/blood-2006-05-023093. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-023093v1 108/13/4170    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 Navas, T. A. Articles by Verma, A. Search for Related Content PubMed PubMed Citation Articles by Navas, T. A. Articles by Verma, A. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Inhibition of overactivated p38 MAPK can restore hematopoiesis in myelodysplastic syndrome progenitors Tony A. Navas, Mani Mohindru, Myka Estes, Jing Ying Ma, Lubomir Sokol, Perry Pahanish, Simrit Parmar, Edwin Haghnazari, Li Zhou, Robert Collins, Irene Kerr, Aaron N. Nguyen, Yin Xu, Leonidas C. Platanias, Alan A. List, Linda S. Higgins, and Amit Verma From the Albert Einstein College of Medicine, Bronx, NY; the University of Texas Southwestern Medical School, Dallas, TX; the Dallas Veterans Affairs Medical Center, Dallas, TX; Scios Inc, Fremont, CA; the Northwestern University Robert H. Lurie Cancer Center, Chicago, IL; and the Moffit Cancer Center, Tampa, FL. The myelodysplastic syndromes (MDSs) are collections of heterogeneous hematologic diseases characterized by refractory cytopenias as a result of ineffective hematopoiesis. Development of effective treatments has been impeded by limited insights into any unifying pathogenic pathways. We provide evidence that the p38 MAP kinase is constitutively activated or phosphorylated in MDS bone marrows. Such activation is uniformly observed in varied morphologic subtypes of low-risk MDS and correlates with enhanced apoptosis observed in MDS hematopoietic progenitors. Most importantly, pharmacologic inhibition of p38 by a novel small molecule inhibitor, SCIO-469, decreases apoptosis in MDS CD34+ progenitors and leads to dose-dependant increases in erythroid and myeloid colony formation. Down-regulation of the dominant p38 isoform by siRNA also leads to enhancement of hematopoiesis in MDS bone marrow progenitors in vitro. These data implicate p38 MAPK in the pathobiology of ineffective hematopoiesis in lowrisk MDS and provide a strong rationale for clinical investigation of SCIO-469 in MDS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. R. Geest and P. J. Coffer MAPK signaling pathways in the regulation of hematopoiesis J. Leukoc. Biol., August 1, 2009; 86(2): 237 - 250. [Abstract] [Full Text] [PDF] C. R. Geest, M. Buitenhuis, E. Vellenga, and P. J. Coffer Ectopic expression of C/EBP{alpha} and ID1 is sufficient to restore defective neutrophil development in low-risk myelodysplasia Haematologica, August 1, 2009; 94(8): 1075 - 1084. [Abstract] [Full Text] [PDF] M. R. Saadatzadeh, K. Bijangi-Vishehsaraei, R. Kapur, and L. S. Haneline Distinct roles of stress-activated protein kinases in Fanconi anemia type C-deficient hematopoiesis Blood, March 19, 2009; 113(12): 2655 - 2660. [Abstract] [Full Text] [PDF] Y.-A. Cao, A. 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