All-trans Retinoic Acid (ATRA) Differentiates Acute Promyelocytic Leukemia Cells Independently of P-Glycoprotein (P-gp) Related Multidrug Resistance

Abstract

Here the relationship between all-trans retinoic acid (ATRA)-resistance and P-glycoprotein (P-gp)-associated multidrug resistance (MDR) is discussed in acute promyelocytic leukemia (APL). First, the remission rates of ATRA therapy are similar in relapsed/refractory APL to the preceding chemotherapy given and in newly diagnosed APL. Second, MDR cDNA-transduced NB4 (NB4/MDR) cells accumulate less Rhodamine-123 (Rhl23) than NB4 cells, but there is no difference in the intracellular ATRA concentration between them. PSC833 or MS209, MDR modifiers, increases the intracellular accumulation of Rh23 in NB4/MDR and APL cells expressing P-gp, but not of ATRA. Third, the expression of CDb, the NBT reduction activity, the proportion of apoptotic cells and the morphology are not different between NB4/MDR and NB4 cells, and 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-resistant APL cells express more P-gp than ATRA-sensitive ones, P-gp and ATRA-resistance seems to exist independently.

Key Words:

• all-trans retinoic acid (ATRA)
• multi-drug resistance (MDR)
• acute promyelocytic leukemia (APL)