[The molecular basis of leukemogenesis caused by MLL gene rearrangements]

Chromosomal translocations at the MLL gene generate chimeric genes of MLL and its partner, thereby causing aggressive acute leukemia. The sequence of the MLL gene was revealed in the early 1990s. Several years later, murine leukemia models using genetic engineering or retroviral gene transfer techniques were established, which spurred basic research on this disease. Since then, a series of technological breakthroughs such as DNA arrays, shRNA library screening, and deep sequencing have provided us with a much deeper understanding of the molecular basis of leukemogenesis caused by MLL mutations. Based on the understanding of these molecular mechanisms, several small molecules that inhibit critical processes of leukemogenesis have been developed as molecularly-targeted drug candidates. I herein review the rapid progress in this research on the molecular mechanisms of MLL-associated leukemia.