Atypical response to all-trans retinoic acid in a der(5)t(5;17) acute promyelocytic leukemia

Typical acute promyelocytic leukemia (APL) is associated with the t(15;17) translocation, expression of a PML/RARA fusion transcript, and responsivene ss to all-trans retinoic acid (ATRA). Rare APL cases implicating the RARA b ut 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 wi th 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 previou sly 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 involve d, as demonstrated by RT-PCR and Southern blot; (2) response to ATRA in vit ro is atypical, as demonstrated by morphological and functional maturation assays; and (3) PML nuclear bodies are not disrupted, as evidenced by immun ofluorescence staining.