However, Meis1 and Pbx3 were activated in Mir142−/− + IDH2R140Q leukemic GMPs, suggesting that synergistic activation of these co-factors may contribute to the leukemogenic effect of our combined mutations in Mir142 and IDH2. Our data, therefore, points to a dual mechanism underpinning the inter-dependence of Mir142 loss-of-function and IDH mutations in AML: antagonistic regulation of HOXA cluster expression and mutual activation of homeobox co-factors. Here, IDH2 is linked to acute myeloid leukemia.