The mammalian Ras proteins, H-, N-and K-Ras, belong to the small GTPase superfamily. They cycle between a GTP-bound active form and a GDP-bound inactive form. 1, 2 The conversion from the GTP-bound form to the GDP-bound form is mediated by the intrinsic GTPase activity of Ras proteins and is greatly accelerated by Ras-associated GAPs (GTPase-activating proteins). Canonical, cancer-associated Ras mutations at codons G12, G13 or Q61 severely compromise the hydrolysis of GTP to GDP, thereby leading to the accumulation of Ras-GTP and hyperactivation of Ras downstream signaling. Mutations in the KRAS and NRAS genes (not in HRAS) are frequently identified in myeloid disorders (15–60%), including acute myeloid leukemia, atypical chronic myeloid leukemia, chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML). 3 In these diseases, the frequency of NRAS mutations is significantly higher than that of