Targeting the MDM2-p53 Interaction with Siremadlin: A Promising Therapeutic Strategy for Treating <i>TP53</i> Wild-Type Chronic Lymphocytic Leukemia.

ABSTRACT: Background: Chronic lymphocytic leukemia (CLL) treatment has transitioned from traditional chemotherapy to more targeted therapies, but challenges such as resistance and suboptimal responses persist. This study aimed to evaluate HDM201, a second-generation MDM2-p53 binding antagonist, as a novel therapeutic strategy for CLL, with a focus on its effectiveness across different TP53 genetic contexts. Methods: We utilized a panel of B cell leukemia-derived cell lines with varying TP53 statuses, including TP53-knockout (KO) derivatives of the human B cell line Nalm-6, and assessed the impact of HDM201 on primary CLL samples with both TP53 wild-type and mutant backgrounds. Results: Our results revealed that TP53 wild-type and heterozygous <

SUBMITTER: Aptullahoglu E 

PROVIDER: S-EPMC11763703 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature