A Novel Acute Promyelocytic Leukemia Model: From Cell to Murine System

Abstract

Differentiation-inducing therapy by all-trans retinoic acid (RA) is now a standard 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 patients 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 novel APL cell line (UF-1) with RA-resistant features. In addition, we have established a human GM-CSF-producing transgenic (hGMTg) SCID mice system. UF-1 cells were inoculated either intraperitoneally or subcutaneously into hGMTg SCID mice and to make the first RA-resistant murine APL model. These RA-resistant APL model systems in vitro and in vivo may be useful for investigating molecular studies on blocking of leukemic cell differentiation and as a means to investigate the mechanisms of RA resistance. Moreover, this murine model system will be important for developing novel therapeutic strategies in RA-resistant APL.