Constitutively active mutants of SHP2 induce oncogenic transformation through activation of the MAPK and PI3K/AKT cascade.51–54PTPN11 mutations have been initially associated with the development of myeloproliferative disorders (MPD), juvenile myelomonocytic leukemia (JMML), and AML.45,51,55–57 More recently, a few studies have shown that single Ptpn11 gain-of-function mutations predispose mice to acute leukemias58,59 suggesting that PTPN11 mutations play a causal role in the development of this disease. This evidence concerns the gene PTPN11 and juvenile myelomonocytic leukemia.