In vitro effect of ATRA, TSA, and HU in various combinations on t(11;17) APL (patient's blasts), t(15;17) primary APL, and ATRA-resistant t(15;17) APL.
Primary blasts from patient's bone marrow at leukemia relapse, from an ATRA-resistant t(15;17) APL patient and from a t(15;17) APL patient at diagnosis were cultured (1.5 to 2 × 106 cells/mL) in RPMI 1640 medium supplemented with 10% fetal calf serum (FCS) and treated with 1 μM ATRA and/or 100 ng/mL TSA for 5 days as described.12 Differentiation of these blasts was evaluated by morphology in Wright-Giemsa–stained cytospins (panels A and B). Original magnifications, × 40. Differentiation was quantified by the nitroblue tetrazolium (NBT) dye reduction assay (panel C) after treatment of blasts with the indicated agents for 5 days in culture. Results are expressed as the average values of the percentages of positive cells evaluated in at least 10 microscopic fields ± SD. (D) Quantitative fluorescence activated cell sorting (FACS) analysis of the differentiation antigen CD11a and CD11b in APL t(11;17) blasts induced by 4 days of treatment with 1 μM ATRA and/or 50 ng/mL TSA.
