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Publication : Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins.

First Author  Ayton PM Year  2001
Journal  Oncogene Volume  20
Issue  40 Pages  5695-707
PubMed ID  11607819 Mgi Jnum  J:72275
Mgi Id  MGI:2152239 Doi  10.1038/sj.onc.1204639
Citation  Ayton PM, et al. (2001) Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. Oncogene 20(40):5695-707
abstractText  The MLL (Mixed Lineage Leukemia) gene is a common target for chromosomal translocations associated with human acute leukemias. These translocations result in a gain of MLL function by generating novel chimeric proteins containing the amino-terminus of MLL fused in-frame with one of 30 distinct partner proteins. Structure/function studies using an in vitro myeloid progenitor immortalization assay have revealed that at least four nuclear partner proteins contribute transcriptional effector properties to MLL to produce a range of chimeric transcription factors with leukemogenic potential. Mouse models suggest that expression of an MLL fusion protein is necessary but not sufficient for leukemogenesis. Interestingly, whilst all MLL fusion proteins tested so far phenocopy each other with respect to in vitro immortalization, the latency period required for the onset of acute leukemia in vivo is variable and partner protein dependent. We discuss potential mechanisms that may account for the ability of distinct MLL fusion proteins to promote short or long latency leukemogenesis.
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