biostudies-literatureUnknown9(1)Khanna VMurine double minute 2 (MDM2) inhibitors have shown promising activity in TP53-wild type tumors and are under active investigation across a spectrum of malignancies. Herein, we report a 51-year-old female with MDM2-amplified, TP53-wild type adenoid cystic carcinoma who was treated with a MDM2 inhibitor and developed persistent pancytopenia despite drug discontinuation. Her pancytopenia was associated with 20 distinct pathogenic TP53 mutations in peripheral blood and bone marrow not present in drug-resistant tumor tissue. Plasma TP53 mutations were similarly detected among 4 other patients treated at our institution, with the number of mutations correlating strongly with duration of treatment. This case suggests that MDM2 inhibitors are associated with TP53 clonal hematopoiesis, which may cNPJ precision oncology34https://www.ebi.ac.uk/biostudies/studies/S-EPMC11790943biostudies-literatureMDM2 inhibition is associated with the emergence of TP53-altered clonal hematopoiesis.PMC11790943Stehr HDiep RKhanna VEslami GReyes RFernandez-Pol SChen CTSuarez CJFord JMPinto HZhang TYfalseMDM2 inhibition is associated with the emergence of TP53-altered clonal hematopoiesis.Murine double minute 2 (MDM2) inhibitors have shown promising activity in TP53-wild type tumors and are under active investigation across a spectrum of malignancies. Herein, we report a 51-year-old female with MDM2-amplified, TP53-wild type adenoid cystic carcinoma who was treated with a MDM2 inhibitor and developed persistent pancytopenia despite drug discontinuation. Her pancytopenia was associated with 20 distinct pathogenic TP53 mutations in peripheral blood and bone marrow not present in drug-resistant tumor tissue. Plasma TP53 mutations were similarly detected among 4 other patients treated at our institution, with the number of mutations correlating strongly with duration of treatment. This case suggests that MDM2 inhibitors are associated with TP53 clonal hematopoiesis, which may c2025-01-01T00:00:00Z2025 Feb2026-06-02T20:04:46.603Z2025-04-04T00:52:20.523ZS-EPMC117909433990098910.1038/s41698-025-00823-x