Thus, as IDH2 mutants develop AML, a mosaic mouse modeling approach for IDH2 mutation was generated by transplanting sub-lethally irradiated mice with HSCs derived from the double KI Flt3-ITD/NrasG12D mutant mice (both mutations being commonly observed in human AML) and previously transduced with retroviral factors expressing Idh2 mutant alleles (Idh2R140Q or Idh2R172K; (57)). Here, IDH2 is linked to acute myeloid leukemia.