IN-VITRO RESPONSE TO ALL-TRANS-RETINOIC ACID OF ACUTE PROMYELOCYTIC LEUKEMIAS WITH NONRECIPROCAL PML RARA OR RARA/PML FUSION GENES/

fusion genes, PML/RARA and RARA/PML, and by its sensitivity to all-tra ns retinoic acid (ATRA) differentiating treatment. Rare APL cases lack ing the t(15;17) have been described. We have previously reported two cases presenting with submicroscopic insertions of RARA or PML into ch romosome 15 or 17, respectively. These insertions lead to the formatio n of potentially functional, nonreciprocal, PML/RARA or RARA/PML fusio n genes, providing the unique opportunity to investigate in a human no ncell-line model the respective role of PML/RARA or RARA/PML in retino id signaling. Here, we report the in vitro response to ATRA of these t wo cases as well as of a third case presenting with submicroscopic ins ertion (15;17) and expressing exclusively PML/RARA, by morphological, functional, and immunological assays. The two cases expressing PML/RAR A presented with an immunostaining pattern typical of APL and a positi ve response to ATRA, whereas the APL case expressing only a RARA/PML f usion transcript exhibited an immunostaining pattern typical of non-AP L cells, and was resistant to ATRA. Our results confirm that sensitivi ty to ATRA requires expression of PML/RARA and strongly correlates wit h immunostaining, and demonstrate that expression of RARA/PML alone is sufficient for a cytological APL phenotype, but does not confer sensi tivity to ATRA. (C) 1998 Wiley-Liss, Inc.