We identified TET2 and PTPN11 mutations in both mouse and human AML and then demonstrated the ability of Tet2 loss and PTPN11 D61Y to initiate leukemogenesis in concert with expression of AML1-ETO in vivo.
Moreover, tissue-specific knock-in of Ptpn11(E76K/+) mutation in lineage-committed myeloid, T lymphoid, and B lymphoid progenitors also results in AML, T-ALL, and B-ALL, respectively.