title: Atypical response to all-trans retinoic acid in a der(5)t(5;17) acute promyelocytic leukemia.
abstract: Typical acute promyelocytic leukemia (APL) is associated with the t(15;17) translocation, expression of a PML/RARA fusion transcript, and responsiveness to all-trans retinoic acid (ATRA). Rare APL cases implicating the RARA but not the PML gene have been reported. Cases with t(11;17)(q23;q21) which fuses the PLZF and RARA genes do not respond to ATRA. In contrast, cases with t(11;17)(q13;q21) and t(5;17)(q35;q21) which fuse RARA with NuMA and NPM, respectively, were reported to be sensitive to ATRA. We described previously an APL case with an unbalanced t(5;17) implicating RARA but neither PML nor PLZF. Here, we show that in this case: (1) the NPM gene is not involved, as demonstrated by RT-PCR and Southern blot; (2) response to ATRA in vitro is atypical, as demonstrated by morphological and functional maturation assays; and (3) PML nuclear bodies are not disrupted, as evidenced by immunofluorescence staining.
authors.affiliation: Department of Biology and Hematology, Institute Paoli-Calmettes, INSERM U119, Marseille, France.
authors.forename: M J
authors.initials: MJ
authors.lastname: Mozziconacci
authors.forename: C
authors.initials: C
authors.lastname: Liberatore
authors.forename: F
authors.initials: F
authors.lastname: Grignani
authors.forename: D
authors.initials: D
authors.lastname: Sainty
authors.forename: P G
authors.initials: PG
authors.lastname: Pelicci
authors.forename: F
authors.initials: F
authors.lastname: Birg
authors.forename: M
authors.initials: M
authors.lastname: Lafage-Pochitaloff
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002467:Cell Nucleus; D002886:Chromosomes, Human, Pair 17; D002895:Chromosomes, Human, Pair 5; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018168:Receptors, Retinoic Acid / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D014178:Translocation, Genetic; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin