The targeting of self-renewal pathways commonly activated in leukemia serves as a potential strategy for multiple subtypes of this disease regardless of genetic, clonal, or cellular heterogeneity. Elevation of β-catenin above physiological conditions enhances the self-renewal of normal hematopoietic stem cells (HSCs) , and this attribute appears to be commonly utilized by leukemia cells.1 Dependency on elevated β-catenin activity in leukemia stem cells (LSCs) demonstrated in several different types of leukemia strongly suggest an essential and universal role for β-catenin in LSC function in leukemia.2-6 Since normal adult HSCs do not require its basal activity,7 β-catenin has emerged as a potential LSC-specific therapeutic target.