In contrast, combined NRasG12D activation and EZH2 deficiency (Mx1-Cre+;NRasG12D+/−;Ezh2f/f, hereafter G12D/E2-KO) significantly accentuated disease progression from indolent to lethal MPN and acute leukemia with a shortened survival (median 86 days and mean 103 ± 53 days; P < 0.0001 vs. G12D or E2-KO; Fig. 1a). This evidence concerns the gene MX1 and acute leukemia.