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Blood, 14 May 2009, Vol. 113, No. 20, pp. 4922-4929. Prepublished online as a Blood First Edition Paper on November 24, 2008; DOI 10.1182/blood-2008-07-170480. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-07-170480v1 113/20/4922    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 Horton, S. J Articles by Williams, O. Search for Related Content PubMed PubMed Citation Articles by Horton, S. J Articles by Williams, O. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 22, 2008 Accepted November 10, 2008 Acute myeloid leukemia induced by MLL-ENL is cured by oncogene ablation despite acquisition of complex genetic abnormalities Sarah J Horton, Vanessa Walf-Vorderwulbecke, Steve J Chatters, Neil J Sebire, Jasper de Boer, and Owen Williams* Molecular Haematology and Cancer Biology Unit, UCL Institute of Child Health and Great Ormond Street Hospital, London, United Kingdom Paediatric Malignancy Cytogenetics Unit, UCL Institute of Child Health and Great Ormond Street Hospital, London, United Kingdom Department of Histopathology, UCL Institute of Child Health and Great Ormond Street Hospital, London, United Kingdom * Corresponding author; email: owen.williams{at}ich.ucl.ac.uk. Chromosomal translocations involving 11q23 are frequent in infant acute leukemia and give rise to the formation of MLL-fusion genes. The mechanism of leukemic transformation by these fusions has been the subject of numerous investigations. However, the dependence of acute leukemia on MLL-fusion activity in vivo and the efficacy of targeting this activity in order to eliminate disease have not been established. We have developed a model for conditional expression of MLL-ENL in hematopoietic progenitor cells, in which expression of the fusion oncogene is turned off by doxycycline. Conditionally immortalized myeloblast cells derived from these progenitors were found to induce leukemia in vivo. Leukemic cells isolated from primary recipient mice were shown to have acquired additional genetic abnormalities and when transplanted into secondary recipients induced leukemia with shortened latencies. However, the leukemic cells remained dependent upon MLL-ENL expression in vitro and in vivo and its ablation resulted in regression of established leukemias. This study demonstrates that even genetically complex leukemias can be reversed upon inactivation of the initiating MLL-fusion and has important implications for the design of novel leukemia therapies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. K. Slany The molecular biology of mixed lineage leukemia Haematologica, July 1, 2009; 94(7): 984 - 993. [Abstract] [Full Text] [PDF]

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