Differentiation of refractory acute promyelocytic leukemia cells by retinoids

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All-trans retinoic acid (ATRA) is a metabolite of vitamin A that is used for molecular targeting therapy of acute promyelocytic leukemia (APL). Most patients with relapse after ATRA therapy show acquired resistance to ATRA, which seems to result from low plasma levels of the drug during therapy. This may be because of increased oxidative catabolism of ATRA or expression of the multi-drug resistance gene product. It is important to discover novel retinoids for refractory APL cells and investigate differentiation mechanisms of APL cells induced by retinoids. In the present study, we examined induced genes of APL cells by ATRA using DNA microarray systems. Increased expression of defensins, bactericidal peptides, were identified. Moreover, defensins genes expression in HL-60 cell line are induced by ATRA.