All-trans retinoic acid (ATRA) differentiates acute promyelocytic leukemiacells independently of P-glycoprotein (P-gp) related multidrug resistance

Here the relationship between all-trans retinoic acid (ATRA)-resistance and P-glycoprotein (P-gp)-associated multidrug resistance (MDR) is discussed i n acute promyelocytic leukemia (APL). First, the remission rates of ATRA th erapy are similar in relapsed/refractory APL to the preceding chemotherapy given and in newly diagnosed A-PL. Second, MDR1 cDNA-transduced NB4 (NB4/MD R) cells accumulate less Rhodamine-123 (Rh123) than N134 cells, but there i s no difference in the intracellular ATRA concentration between them. PSC83 3 or MS209, MDR modifiers, increases the intracellular accumulation of Rh12 3 in NB4/MDR and APL cells expressing P-gp, but not of ATRA. Third, the exp ression of CD11b, the NBT reduction activity, the proportion of apoptotic c ells and the morphology are not different between NB4/MDR and NB4 cells, an d between APL cells expressing P-gp and not. APL cells express little P-gp, and mainly express CD33 but no CD34. Despite previous reports that ATRA-re sistant APL cells express more P-gp than ATRA-sensitive ones, P-gp and ATRA -resistance seems to exist independently.