CDK4/6 inhibition mitigates chemotherapy-induced expansion of TP53-mutant clonal hematopoiesis - PubMed
14 hours ago
- #chemotherapy
- #CDK4/6 inhibition
- #clonal hematopoiesis
- CDK4/6 inhibitor trilaciclib mitigates chemotherapy-induced expansion of TP53-mutant clonal hematopoiesis (CH).
- Individuals with pre-existing TP53 CH are at high risk of therapy-related myeloid neoplasm (tMN).
- Trilaciclib, when given with chemotherapy, reduces expansion of CH clones with DNA damage response gene mutations, including TP53.
- A syngeneic mouse model confirmed CDK4/6 inhibition blocks platinum-induced TP53 competitive repopulation by promoting hematopoietic stem and progenitor quiescence.
- This study provides proof of concept for a pharmacologic strategy to prevent chemotherapy-driven expansion of preleukemic TP53-mutant clones.