UNBALANCED TRANSLOCATION T(5-17) IN AN ATYPICAL ACUTE PROMYELOCYTIC LEUKEMIA

Acute promyelocytic leukemia (APL; M3 in the FAB classification) is sp ecifically associated with the t(15;17)(q23;q12) and the consequent fo rmation of a PML/RARA fusion gene. A few cases of APL with a t(11;17)( q23;q12) and a PLZF/RARA fusion gene have recently been reported. In a ddition, a new variant, t(5;17)(q32;q12), with a RARA rearrangement wa s described in a child with atypical APL. We report an unbalanced der( 5)t(5;17) in an atypical APL case showing unusual dysgranulopoiesis an d some M2 features. The breakpoints were difficult to localize precise ly on chromosome 5, because the translocation may have occurred on a p revious del(5q). The karyotype also showed del(8q) and multiple double -minutes (dmin). Molecular studies evidenced RARA rearrangement but sh owed neither PML rearrangement nor PML/RARA fusion. Fluorescence in si tu hybridization revealed that the dmin were of chromosome 8 origin an d that they accounted for the MYC amplification observed in Southern b lots. The patient did very poorly despite chemotherapy and all-trans r etinoic acid (ATRA) treatment. Thus, the t(5;17) could represent a sec ond type of variant translocation in APL that, like the disease associ ated with t(11;17), does not seem to respond to ATRA therapy. Whereas RARA rearrangement appears sufficient for an APL-like phenotype, it se ems that the presence of a classical PML/RARA is required for typical APL with response to ATRA.