Aberrant PRAME expression in CD34⁺ normal hematopoietic progenitors inhibits myeloid differentiation. (A-C) The numbers of cells in culture expressing CD34 (A), CD117 (B), and CD11b (C) are shown over time in PRAME vector–transduced cells compared with control vector–transduced cells in the absence of ATRA. The data shown represent the mean of 3 independent experiments. On day 0 there were 100 000 cells in culture for each condition. The early precursor cell markers, CD34 and CD117 (P = .001 and P = .002, respectively), were more highly expressed in PRAME cells and the terminal myeloid marker, CD11b (P = .04), demonstrated lower expression in PRAME cells compared with control vector–transduced cells over time. (D-I) The consequences of ATRA exposure on percentage of CD117 and CD11b expression over time are shown. In the absence of ATRA, PRAME-expressing cells, compared with control cells, exhibited up to 41% greater expression of CD117 and 35% lower expression of CD11b (D,G). These differences persisted in PRAME cells exposed to low (physiologic) concentrations of ATRA (0.001 μM; E,H), but were overcome with increasing concentrations of ATRA of 0.01 μM (F,I; CD117 [P = .02] and CD11b [P = .15]). However, as shown in panel F, PRAME cells expressed increased CD117 early in culture between days 0 and 7, compared with later in culture for cells exposed to no ATRA or 0.001 μM ATRA concentrations (D-E).