The 'Yamanaka factors' (Oct4, Sox2, Klf4 and c-Myc) are able to generate induced 
pluripotent stem (iPS) cells from different cell types. However, to what degree 
primary malignant cells can be reprogrammed into a pluripotent state has not 
been vigorously assessed. We established an acute myeloid leukemia (AML) model 
by overexpressing the human mixed-lineage leukemia-AF9 (MLL-AF9) fusion gene in 
mouse hematopoietic cells that carry Yamanaka factors under the control of 
doxycycline (Dox). On addition of Dox to the culture, the transplantable 
leukemia cells were efficiently converted into iPS cells that could form 
teratomas and produce chimeras. Interestingly, most chimeric mice spontaneously 
developed the same type of AML. Moreover, both iPS reprogramming and leukemia 
reinitiation paths could descend from the same leukemia-initiating cell. RNA-seq 
analysis showed reversible global gene expression patterns between these 
interchangeable leukemia and iPS cells on activation or reactivation of MLL-AF9, 
suggesting a sufficient epigenetic force in driving the leukemogenic process. 
This study represents an important step for further defining the potential 
interplay between oncogenic molecules and reprogramming factors during MLL 
leukemogenesis. More importantly, our reprogramming approach may be expanded to 
characterize a range of hematopoietic malignancies in order to develop new 
strategies for clinical diagnosis and treatment.