E7820, an anti-cancer sulfonamide, degrades RBM39 in patients with splicing factor mutant myeloid malignancies: a phase II clinical trial
Jan Philipp Bewersdorf, Maximilian Stahl, Justin Taylor, Xiaoli Mi, Namrata S. Chandhok, Justin M. Watts, Andriy Derkach, Mateusz Wysocki, Sydney X. Lu, Jessie Bourcier, Simon J. Hogg, Jahan Rahman, Sana Chaudhry, Tulasigeri M. Totiger, Omar Abdel‐Wahab, Eytan M. Stein
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 ].