Reduced leukemogenic capacity of Myc^V394D-AML cells compared with Myc-AML cells. (A) MSCV/Cre^ERTMyc^fx/fx, Myc/Cre^ERTMyc^fx/fx, or Myc^V394D/Cre^ERTMyc^fx/fx AML cells were transplanted into different groups of recipient mice. Starting on day 3 after transplantation, mice were treated with vehicle (Veh) or TAM daily for 5 consecutive days to induce the deletion of endogenous Myc. The mice were monitored for leukemia development and leukemia-related death. (B-E) Myc-GFP and Myc^V394D-GFP AML cells were collected from the mice that had leukemia (above) and the differentiation status of these cells was assessed by morphologic study for leukemic blasts (B) and c-Kit expression (C); the self-renewal capacity of LSCs was analyzed by serial transplantation (D). The frequency of LSCs was examined by serial dilution and competitive transplantation assay (E). *P < .05; **P < ..01 compared with vehicle groups in panel A, and Myc groups in panels B-D. ^##P < .01 compared with Myc^V394D second transplantation.