Recent studies have shown that CDK6 is a cell-cycle regulator and critical effector of MLL fusions and it is responsible for a myeloid differentiation block, making it an actionable target for overcoming the traditional drug resistance typical of MLL-rearranged AML [27]/Together with CDK6, also DOT1L, a histone methyltransferase involved in differentiation and proliferation of hematopoietic stem cells (HSCs), has been recently identified as a putative target in this AML subtype [28,29]. Here, PRDM9 is linked to acute myeloid leukemia.