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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3876-3882. Prepublished online as a Blood First Edition Paper on January 29, 2004; DOI 10.1182/blood-2003-11-3817. This Article Full Text (PDF) All Versions of this Article: 2003-11-3817v1 103/10/3876    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 Eguchi, M. Articles by Greaves, M. Search for Related Content PubMed PubMed Citation Articles by Eguchi, M. Articles by Greaves, M. Social Bookmarking                   What's this? Submitted November 7, 2003 Accepted December 22, 2003 The small oligomerization domain of Gephyrin converts MLL to an oncogene Mariko Eguchi, Minenori Eguchi-Ishimae, and Mel Greaves* Leukaemia Research Fund Centre, Institute of Cancer Research, London, United Kingdom * Corresponding author; email: mel.greaves{at}icr.ac.uk. The MLL gene forms chimeric fusions with a diverse set of partner genes as a consequence of chromosome translocations in leukemia. In several fusion partners, a transcriptional activation domain appears to be essential for conferring leukemogenic capacity on MLL. Other fusion partners, however, lack such domains. Here we show that Gephyrin (GPHN), a neuronal receptor assembly protein and rare fusion partner of MLL in leukemia, has the capacity as an MLL-GPHN chimera to transform hematopoietic progenitors, despite lack of transcriptional activity. A small 15 amino-acid tubulin-binding domain of GPHN is necessary and sufficient for this activity in vitro and in vivo. This domain also confers oligomerization capacity on MLL protein suggesting that such activity may contribute critically to leukemogenesis. The transduction of MLL-GPHN into hematopoietic progenitor cells caused myeloid and lymphoid lineage leukemias in mice, suggesting that MLL-GPHN can target multipotent progenitors cells. Our results, and other recent data, provide a mechanism for oncogenic conversion of MLL by fusion partners encoding cytoplasmic proteins. 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]

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