DIFFERENTIATION OF T(5-17) VARIANT ACUTE PROMYELOCYTIC LEUKEMIC BLASTS BY ALL-TRANS-RETINOIC ACID

All-trans retinoic acid (ATRA) induces differentiation of acute promye locytic leukemic (APL) blasts from patients with t(15;17) APL. However , blasts from patients with the t(11;17) variant do not differentiate in response to ATRA. Our group has identified a variant of APL charact erized by t(5;17) and expression of the NPM-RAR fusion gene product. F rom case reports it has been difficult to establish whether ATRA induc es clinical responses in patients with this variant. In order to deter mine whether t(5;17) blasts differentiate with ATRA, we harvested mono nuclear bone marrow cells from a patient with t(5;17) APL at time of r elapse and cultured them in medium containing ATRA. Morphologic analys is of cytospins after 7 days of culture revealed that 60% of cells in the ATRA-treated culture had differentiated into mature neutrophilic f orms, as opposed to less than 1% in the control culture. Seventy-three percent of cells acquired NET positivity after exposure to ATRA, comp ared with 1% in the control culture. These results indicate that t(5;1 7) blasts retain the ability to terminally differentiate in response t o retinoic acid.