Venetoclax overcomes resistance to all-trans retinoic acid in a variant acute promyelocytic leukemia with TNRC18::RARA fusion.

ABSTRACT

Acute promyelocytic leukemia (APL) is generally driven by PMLRARA, but approximately 2% of variant APL patients do not contain this fusion gene and pose challenges in diagnosis and treatment. Here, we reported an aggressive APL patient with variant TNRC18RARA fusion gene, who was resistant to standard differentiation induction therapy consisting of all-trans retinoic acid (ATRA) and arsenic trioxide but achieved complete remission with venetoclax plus ATRA. Mechanistically, venetoclax possesses synergistic effects in ATRA-induced TNRC18RARA-positive cell differentiation.