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This Article Full Text Full Text (PDF) 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 Hess, J. L. Articles by Korsmeyer, S. J. Search for Related Content PubMed PubMed Citation Articles by Hess, J. L. Articles by Korsmeyer, S. J. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Defects in Yolk Sac Hematopoiesis in Mll-Null Embryos Jay L. Hess, Benjamin D. Yu, Bin Li, Rob Hanson, and Stanley J. Korsmeyer From the Howard Hughes Medical Institute, the Division of Molecular Oncology, the Departments of Medicine and Pathology, Washington University School of Medicine, St Louis, MO. Translocations involving the mixed lineage leukemia gene (MLL ), the human homolog of the Drosophila gene trithorax, are one of the most common genetic alterations in human acute leukemias. Each translocation involving MLL results in loss of one functional copy of MLL and the generation of a chimeric fusion protein with potential dominant negative or neomorphic activity. Mll is a positive regulator of Hox genes, which have been implicated in both axial skeleton patterning and hematopoietic development. Previous studies indicated that Hox gene expression is altered in Mll heterozygous (+/-) and homozygous (-/-) deficient mice. To study the role of Mll in hematopoiesis and to obtain insights into leukemogenesis, we have examined the effects of haplo-insufficiency or absence of Mll by in vitro differentiation of Mll +/+, +/-, and -/- yolk sac progenitor cells. Mll -/- colonies were fewer in number, took longer to develop, and contained fewer cells than their wild-type and heterozygous counterparts. Formation of colony-forming unit-granulocyte, erythroid, macrophage, megakaryocyte (CFU-GEMM), colony-forming unit-macrophage (CFU-M), and burst-forming unit-erythroid (BFU-E) was markedly decreased in Mll -/- cultures, while numbers of colony-forming unit-erythroid (CFU-E), colony-forming unit-granulocyte (CFU-G), and colony-forming unit-granulocyte macrophage (CFU-GM) were essentially unaffected. Despite the decreased numbers of colonies present, Mll -/- cultures showed all cell types without morphologic evidence of maturation arrest. These studies indicate that Mll is required for normal numbers of hematopoietic progenitors and their proper differentiation, especially along the myeloid and macrophage pathways. Blood, Vol. 90 No. 5 (September 1), 1997: pp. 1799-1806 © 1997 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: M. Liedtke and M. L. Cleary Therapeutic targeting of MLL Blood, June 11, 2009; 113(24): 6061 - 6068. [Abstract] [Full Text] [PDF] R. Popovic, L. E. Riesbeck, C. S. Velu, A. Chaubey, J. Zhang, N. J. Achille, F. E. Erfurth, K. Eaton, J. Lu, H. L. Grimes, et al. Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization Blood, April 2, 2009; 113(14): 3314 - 3322. [Abstract] [Full Text] [PDF] I. Maillard, Y.-X. Chen, A. Friedman, Y. Yang, A. T. Tubbs, O. Shestova, W. S. Pear, and X. 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