Germline homologous recombination deficiency influences TP53-mutant clonal hematopoiesis fitness during platinum and PARP inhibitor treatment.

Germline HRD reduces clonal hematopoiesis expansion during platinum and PARP inhibitor treatment in patients with TP53-mutant CH.

• Why it matters: Understanding factors that influence therapy-related myeloid neoplasms (tMN) risk is crucial, as CH driven by DNA damage response mutations is a common precursor.
• What they did: The study analyzed serial blood samples from patients treated with carboplatin and PARPi, finding DDR CH expansion was largely reduced in germline HRD carriers, and validated these results in a Trp53-mutant mouse model.
• The result: Findings suggest that prior therapies like carboplatin and germline HRD status may modulate tMN risk, potentially informing personalized treatment strategies to mitigate this risk.