Figure 1
Increased survival of APL mice by treatment with pVAX14 in addition to ATO and ATRA. (a) Kaplan–Meier survival curves showing increased survival in the APL mice; pVAX14+ATO+ATRA showed the best survival with significant difference compared with Vehicle+ATO+ATRA (P<0.03). The differences between pVAX14+ATO+ATRA or Vehicle+ATO+ATRA and Placebo were significant (P<0.0001); the schematic diagram of the protocol used is illustrated. APL blast cells from the spleen (104) were injected intravenously on day 0 (D0), followed by ATRA (5-mg–21-day release pellet, Innovative Research of America, Sarasota, FL, USA) on day 6 (D6). Vehicle (Hepes buffered saline solution) or pVAX14 DNA (2 × 50 μg) was administered intramuscularly on day 7 (D7) and every 20 days for a total of 3 cycles. ATO was prepared (Sigma Chemical Co, St Louis, MO, USA)3 and administered intraperitoneally daily at the concentration of 5 μg/g/mice for 28 consecutive days starting on D6. (b) Minimal residual disease (MRD) in APL mice treated with pVAX14+ATO+ATRA. Primer sequences are detailed in Supplementary Table S3. Results were expressed as normalized copy numbers (NCN) of PML-RARA transcripts using Abl as a housekeeping gene.8, 10 A significant reduction in MRD was observed on day 60 (D60) of pVAX14+ATO+ATRA-treated APL mice compared with Vehicle+ATO+ATRA (P<0.04) mice (inset); pVAX14+ATO+ATRA or Vehicle+ATO+ATRA versus placebo were significantly different (P<0.01). (c) Detection of significantly increased MyD88 expression on day 40 (D40) of pVAX14+ATO+ATRA-treated APL mice compared with Vehicle+ATO+ATRA-treated mice (P<0.017). Primer sequences are shown in Supplementary Table S3. The nonparametric, unpaired, two-tailed, Mann–Whitney test was used to compare different groups using the Prism software.
