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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2508-2511. Prepublished online as a Blood First Edition Paper on July 10, 2008; DOI 10.1182/blood-2008-01-134338. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-01-134338v1 112/6/2508    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 CrossRef Google Scholar Articles by Dorrance, A. M. Articles by Caligiuri, M. A. PubMed PubMed Citation Articles by Dorrance, A. M. Articles by Caligiuri, M. A. Related Collections Neoplasia Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief Report The Mll partial tandem duplication: differential, tissue-specific activity in the presence or absence of the wild-type allele Adrienne M. Dorrance1,2, Shujun Liu1, Anita Chong1, Benjamin Pulley1, David Nemer1, Martin Guimond1, Weifeng Yuan1, Dennis Chang1, Susan P. Whitman1,3, Guido Marcucci1,3, and Michael A. Caligiuri13 1 Department of Internal Medicine, Division of Hematology and Oncology; 2 Department of Veterinary Biosciences, and 3 Comprehensive Cancer Center–James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus The partial tandem duplication of MLL (MLL-PTD) is found in 5% to 10% of patients with acute myeloid leukemia (AML) and normal cytogenetics. Its expression in leukemic blasts is coincident with a silenced wild-type (WT) MLL allele. We therefore generated mice expressing the Mll-PTD in the absence of Mll-WT. These MllPTD/– mice die at birth unlike the normal life expectancy of MllPTD/WT, MllWT/–, and MllWT/WT mice. Using MllWT/WT fetal liver cells (FLC) as baseline, we compared MllPTD/– with MllPTD/WT FLC and found both had increased HoxA gene expression and granulocyte-macrophage colony-forming progenitor cells (CFU-GM); in contrast, only MllPTD/WT FLC had increased pluripotent hemopoietic progenitors (CFU-GEMM). The similarities between MllPTD/WT and MllPTD/– mice suggest that the Mll-PTD mutation can up-regulate target genes in a dominant, gain-of-function fashion. The differences between these 2 genotypes suggest that in select tissues the Mll-PTD requires cooperation with the Mll-WT in the genesis of the observed abnormality. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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