Altogether, it is for the first time we report that SP1049C therapy decreases the tumorigenicity and aggressiveness of cancer cells in vivo, suppresses the Wnt-β-catenin signaling activation and BCRP overexpression, differentially alters the DNA methylation profiles, as well as depletes the tumorigenic cell subpopulations in murine leukemia model. Here, ABCG2 is linked to leukemia.