Submitted December 30, 2008
Accepted March 5, 2009
Therapeutic targeting of MLL
Michaela Liedtke and Michael L. Cleary*
Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States
* Corresponding author; email: mcleary{at}stanford.edu.
Treatment of hematological malignancies is evolving from a uniform approach to targeted therapies directed at the underlying molecular abnormalities of disease. The Mixed Lineage Leukemia (MLL) proto-oncogene is a recurrent site of genetic rearrangements in acute leukemias, and since its discovery in 1992 many advances have been made in understanding its role in leukemogenesis. A variety of MLL-translocation partners have been described, and detailed structure/function studies have identified functional domains that are required for transformation. Proteins associated with the MLL-core complex or its fusion partners have been isolated and characterized for their critical roles in leukemia pathogenesis. Downstream mediators of MLL-transcriptional regulation and multiple collaborating signaling pathways have been described and characterized. These advances in our understanding of MLL-related leukemogenesis provide a foundation for ongoing and future efforts to develop novel therapeutic strategies that will hopefully result in better treatment outcomes.
