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 Blood, 15 September 2006, Vol. 108, No. 6, pp. 1972-1974.
Prepublished online as a Blood First Edition Paper on May 25, 2006; DOI 10.1182/blood-2006-03-013177.

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Submitted March 28, 2006
Accepted May 2, 2006

Frequent antibody production against RAR{alpha} in both APL mice and patients

Marie Robin, Juliette Andreu-Gallien, Marie-Helene Schlageter, Djaouida Bengoufa, Isabelle Guillemot, Katerina Pokorna, Carine Robert, Jerome Larghero, Philippe Rousselot, Emmanuel Raffoux, Herve Dombret, Pierre Fenaux, Marika Pla, Dominique Charron, Rose-Ann Padua, and Christine Chomienne*

INSERM UMR S 718, Institut Universitaire d'Hematologie (IUH), Paris, France
Laboratoire d'Immunologie et d'Histocompatibilite, AP-HP, Hopital Saint-Louis, Paris, France
Service d'Hematologie, AP-HP, Hopital Saint-Louis, Paris, France
Service d'Hematologie, AP-HP, Hopital Avicenne, Bobigny, France
INSERM UMR S 662, Universite Paris 7, France

* Corresponding author; email: christine.chomienne{at}sls.ap-hop-paris.fr.

In an acute promyelocytic leukemia (APL) transplantable mouse model, we previously reported the presence of antibodies recognizing PML-RAR{alpha} and RAR{alpha} in the sera of ATRA-treated mice. To evaluate this immune response, we determined the prevalence of anti-RAR{alpha} 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 APL patients using a specific Enzyme-Linked-Immunosorbent-Assay (ELISA). In APL mice, significantly higher antibody levels were observed at the latest time-points (days 48-58 levels superior to days 15-18 or days 28-38 levels). Antibody levels were higher in ATRA-treated mice than in placebo-treated mice and were also predictive of better survival. In the APL patients, anti-RAR{alpha} antibodies were detected at diagnosis and after maintenance therapy, reminiscent of the ATRA-treated APL mice. Antinuclear or anti-neutrophil cytoplasmic auto-antibodies were also detected. These data reveal for the first time that in APL patients an immune response may be detected at diagnosis and enhanced after maintenance therapy.


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