Acute myeloid leukemia (AML) is a rapidly lethal blood cancer characterized by aberrant proliferation and differentiation of myeloid progenitors in the hematopoietic tissue. In recent decades, AML patients are significantly increased. In 2019 alone, 21,450 new AML cases were diagnosed in the United States, with an estimated 10,920 deaths due to AML. What's worse, AML occurs with an increasing incidence with advanced age, and the survival rate remains dismal with a median overall survival of only 5–10 months. Notwithstanding great advances in allogenic transplant and chemotherapy, the therapeutic outcomes are unfavorable due to the disease relapse and mortality rates. More importantly, the development of more specific and effective therapies was hampered in part by the lack of proper animal models for AML. Thus, management and elucidation of the pathological mechanism of AML remain an ongoing challenge, and the development of effective AML mouse models and treatment options are urgently needed.