Frequent antibody production against RAR in both APL mice and patients

In an acute promyelocytic leukemia (APL)– transplantable mouse model, we previously reported the presence of antibodies recognizing PML-RAR and RAR in the sera of ATRA-treated mice. To evaluate this immune response, we determined the prevalence of anti-RAR antibodies in a cohort of 48 APL mice, treated by ATRA (n 24) or by placebo pellets (n 24), and in a preliminary subset of 9 patients with APL using a specific enzyme-linked immunosorbent assay (ELISA). In APL mice, significantly higher antibody levels were observed at the latest time points (day 48 to 58 levels superior to day 15 to 18 or day 28 to 38 levels). Antibody levels were higher in ATRA-treated mice than in placebo-treated mice and were also predictive of better survival. In the patients with APL, anti-RAR antibodies were detected at diagnosis and after maintenance therapy, reminiscent of the ATRAtreated APL mice. Antinuclear or antineutrophil cytoplasmic autoantibodies were also detected. These data reveal for the first time that in patients with APL an immune response may be detected at diagnosis and enhanced after maintenance therapy. (Blood. 2006;108: 1972-1974)