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Blood, 19 March 2009, Vol. 113, No. 12, pp. 2826-2834. Prepublished online as a Blood First Edition Paper on January 9, 2009; DOI 10.1182/blood-2008-09-180596. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-09-180596v1 113/12/2826    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 Cheng, E.-c. Articles by Krause, D. S. Search for Related Content PubMed PubMed Citation Articles by Cheng, E.-c. Articles by Krause, D. S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 22, 2008 Accepted December 14, 2008 Role for MKL1 in megakaryocytic maturation Ee-chun Cheng, Qing Luo, Emanuela M. Bruscia, Matthew J. Renda, James A. Troy, Stephanie A. Massaro, David Tuck, Vincent Schulz, Shrikant M. Mane, Nancy Berliner, Yi Sun, Stephan W. Morris, Caihong Qiu, and Diane S. Krause* Department of Laboratory Medicine, Yale University, New Haven, CT, United States College of Bioengineering, Chongqing University, Chongqing, China, United States Department of Pediatrics, Yale University, New Haven, CT, United States Department of Pathology, Yale University, New Haven, CT, United States W. M. Keck Facility, Yale University, New Haven, CT, United States Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States Departments of Pathology and Oncology, St. Jude Children's Research Hospital, Memphis, TN, United States Yale Human Embryonic Stem Cell Core, Yale Stem Cell Center, Yale University, New Haven, CT, United States * Corresponding author; email: diane.krause{at}yale.edu. Megakaryoblastic leukemia 1 (MKL1), identified as part of the t(1;22) translocation specific to acute megakaryoblastic leukemia, is highly expressed in differentiated muscle cells and promotes muscle differentiation by activating serum response factor (SRF). Here we show that MKL1 expression is upregulated during murine megakaryocytic differentiation, and that enforced overexpression of MKL1 enhances megakaryocytic differentiation. When the Human Erythroleukemia (HEL) cell line is induced to differentiate with TPA (12-O-tetradecanoylphorbol 13-acetate), overexpression of MKL1 results in an increased number of megakaryocytes with a concurrent increase in ploidy. MKL1 overexpression also promotes megakaryocytic differentiation of primary human CD34+ cells cultured in the presence of thrombopoietin. The effect of MKL1 is abrogated when SRF is knocked down, suggesting that MKL1 acts through SRF. Consistent with these findings in human cells, knock out of MKL1 in mice leads to reduced platelet counts in peripheral blood, and reduced ploidy in bone marrow megakaryocytes. In conclusion, MKL1 promotes physiological maturation of human and murine megakaryocytes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Gilles, D. Bluteau, S. Boukour, Y. Chang, Y. Zhang, T. Robert, P. Dessen, N. Debili, O. A. Bernard, W. Vainchenker, et al. MAL/SRF complex is involved in platelet formation and megakaryocyte migration by regulating MYL9 (MLC2) and MMP9 Blood, November 5, 2009; 114(19): 4221 - 4232. [Abstract] [Full Text] [PDF]

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