A novel retinoic acid-resistant acute promyelocytic leukemia model in vitro and in vivo (review)

Differentiation-inducing therapy by all-trans retinoic acid (RA) is now a s tandard therapy in patients with acute promyelocytic leukemia (APL). Nearly all patients achieve complete remission by the treatment of all-trans RA, however, clinical remissions are usually of brief duration, and these patie nts often develop RA-resistant disease. The mechanisms of RA-resistance in APL cells are poorly understood and most clinical approaches have not been successful in overcoming RA-resistance. We have recently established a nove l APL cell line (UF-1) with RA-resistant features. In addition, we have est ablished human GM-CSF-producing transgenic (hGMTg) SCID mice system. UF-1 c ells were inoculated either intraperitoneally or subcutaneously into hCMTg SCID mice and made the first RA-resistant murine APL model. These RA-resist ant APL model systems in vitro, and in vivo may be useful for investigating the molecular studies on the block of leukemic cell differentiation and as means to investigate the mechanisms of RA-resistance. Moreover, this murin e model system will be important for developing novel therapeutic strategie s in RA-resistant APL.