E7820, an anti-cancer sulfonamide, degrades RBM39 in patients with splicing factor mutant myeloid malignancies: a phase II clinical trial

Abstract

Treatment options for relapsed and/or refractory (R/R) MDS and AML are limited. Mutations in genes encoding RNA splicing factors are encountered frequently in patients with AML and in up to 60% of MDS patients [ 1 , 2 ]. As splicing factor mutations are often mutually exclusive, splicing factor-mutant cells could be dependent on residual wild-type splicing for survival [ 3 , 4 ]. Targeting residual splicing function could therefore lead to synthetic lethality and constitute a potent therapeutic approach to splicing factor-mutant AML/MDS [ 5 ].