Targeting HASPIN kinase disrupts SR protein-mediated RNA splicing and synergizes with BCL-2 inhibitor venetoclax in AML.

ABSTRACT: Acute myeloid leukemia (AML) is a blood cancer complicated by acquired drug resistance, disease relapse, and low overall survival rates. Combination therapies using multiple targeted inhibitors have been effective in treating patients with AML. However, combination treatments are limited by the number of usable targets and our ability to create rational pairings using complimentary molecular mechanisms. Here, we used a human kinase domain-targeted CRISPR screen to identify histone H3-associated protein (HASPIN) kinase as a significant, understudied dependency in AML. HASPIN depletion significantly reduced growth rate, induced a cell cycle arrest, and dysregulated transcription in AML. A proteomics data mining study characterized serine and arginine repeat enriched splicing factors (SR prot

SUBMITTER: Liu M 

PROVIDER: S-EPMC12304681 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature