Menin-MLL inhibitors block oncogenic transformation by MLL fusion proteins in a fusion partner independent manner

Chromosomal rearrangements of the Mixed Lineage Leukemia (MLL) gene result in fusion proteins which retain the N-terminal portion of MLL fused with one of more than 70 different fusion partners. The high diversity of MLL fusion partners raises a question whether it is possible to develop a general therapeutic strategy to block the oncogenic activity of MLL fusion proteins in a fusion partner independent manner. We have demonstrated that blocking the menin-MLL interaction using small molecule inhibitor inhibits oncogenic activity of different MLL fusion proteins according to a mechanism that is independent on the fusion partner. MLL-AF9, MLL-AF6 and MLL-AF1P transformed cells were treated with the menin-MLL inhibitor MI-2-2