The RBM39 degrader indisulam inhibits acute megakaryoblastic leukemia by altering the alternative splicing of ZMYND8.

ABSTRACT:

Background

Acute megakaryoblastic leukemia (AMKL) is a rare hematological malignancy in adults but children. Alternative splicing (AS) has been shown to affect hematological cancer progression, making splicing factors promising targets. Our research aims to investigate the efficacy of the molecular glue degrader indisulam, which targets the splicing factor RNA binding motif protein 39 (RBM39) in AMKL models.

Results

Public drug sensitivity data analysis revealed that AMKL cell lines exhibited the highest sensitivity to indisulam compared with other tumor types. Then we confirmed that RBM39 depletion by indisulam treatment induced AMKL cell cycle arrest and apoptosis. In AMKL mouse model, indisulam treatment significantly reduced the leukemic burden and prolonged the lifetime

SUBMITTER: Yang Y 

PROVIDER: S-EPMC11995665 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature