MLL1 and menin: not partners in crime?

摘要

The MLL gene encodes a DNA-binding protein that methylates histone H3 lysine 4 (H3K4) and regulates gene expression including multiple Hox genes. Leukemogenic MLL translocations encode MLL fusion proteins (MLL-FPs) that have lost H3K4 methyltransferase activity. An important feature of MLL-FPs is their ability to transform hematopoietic cells into leukemia stem cells. At least 52 functionally diverse MLL-FPs have been described. Fusions with the nuclear proteins AF4, AF9, AF10, ENL, and ELL account for most of MLL-rearranged leukemia. Translocations disrupting the MLL1 gene occur frequently in infant and secondary acute leukemia. MLL1 translocations encode fusion proteins (MLLl-FPs) retaining the N terminus of MLL 1, which interacts with the tumor suppressor menin.2 Indeed, several studies have demonstrated that MLLl-FPs require menin interaction for leukemogenesis.