title: Frequent antibody production against RARalpha in both APL mice and patients.
abstract: In an acute promyelocytic leukemia (APL)-transplantable mouse model, we previously reported the presence of antibodies recognizing PML-RARalpha and RARalpha in the sera of ATRA-treated mice. To evaluate this immune response, we determined the prevalence of anti-RARalpha 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-RARalpha antibodies were detected at diagnosis and after maintenance therapy, reminiscent of the ATRA-treated 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.
authors.affiliation: INSERM UMR S 718, Institut Universitaire d'Hématologie (IUH), Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, Paris Cedex 10, F-75475 France.
authors.forename: Marie
authors.initials: M
authors.lastname: Robin
authors.forename: Juliette
authors.initials: J
authors.lastname: Andreu-Gallien
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Schlageter
authors.forename: Djaouida
authors.initials: D
authors.lastname: Bengoufa
authors.forename: Isabelle
authors.initials: I
authors.lastname: Guillemot
authors.forename: Katerina
authors.initials: K
authors.lastname: Pokorna
authors.forename: Carine
authors.initials: C
authors.lastname: Robert
authors.forename: Jerome
authors.initials: J
authors.lastname: Larghero
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Raffoux
authors.forename: Herve
authors.initials: H
authors.lastname: Dombret
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: Marika
authors.initials: M
authors.lastname: Pla
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Rose-Ann
authors.initials: RA
authors.lastname: Padua
authors.forename: Christine
authors.initials: C
authors.lastname: Chomienne
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000276:immunology; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D018168:Receptors, Retinoic Acid / Q000276:immunology*; D000072482:Retinoic Acid Receptor alpha; D013997:Time Factors; D014212:Tretinoin / Q000627:therapeutic use
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000974:Antibodies, Antinuclear; D000970:Antineoplastic Agents; D001323:Autoantibodies; C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin