A revised model of treatment outcomes in APL. Low RA doses (right) induce differentiation of the bulk of the tumor without affecting the LICs, leading to transient clinical responses but no cure in patients. Arsenic treatment (left) entails some differentiation and substantial loss of LICs, resulting in tumor regression and durable remissions with a high proportion of definitively cured patients. The combination of arsenic and RA, as well as high RA concentrations (bottom) elicit both complete differentiation of leukemia blasts and eradication of LICs, thus leading to strong tumor regression and ultimately to cure in most patients.