A MENage à Trois in Leukemia

Menin binds to the N terminus of the chromatin-remodeling histone methyltransferase MLL and is essential for the transforming activity of at least several oncogenic MLL fusion proteins. In this issue, Yokoyama and Cleary (2008) show that meninʹs essential, and perhaps only, contribution to leukemia is to tether a third protein, LEDGF—a chromatin-associated protein implicated in leukemia and several other disease states—to MLL. Thus, this study identifies a new, critical player in leukemias caused by MLL fusion proteins and defines the biochemical function of menin in the MLL complex.