Frequent antibody production against RARalpha in both APL mice and patients.
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.
Robin
Marie
M
INSERM UMR S 718, Institut Universitaire d'Hématologie (IUH), Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, Paris Cedex 10, F-75475 France.
Andreu-Gallien
Juliette
J
Schlageter
Marie-Helene
MH
Bengoufa
Djaouida
D
Guillemot
Isabelle
I
Pokorna
Katerina
K
Robert
Carine
C
Larghero
Jerome
J
Rousselot
Philippe
P
Raffoux
Emmanuel
E
Dombret
Herve
H
Fenaux
Pierre
P
Pla
Marika
M
Charron
Dominique
D
Padua
Rose-Ann
RA
Chomienne
Christine
C
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
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