Clinicopathologic characteristics of somatic <i>TP53</i> mutations in Philadelphia chromosome–negative myeloproliferative neoplasms: A systematic review and pooled analysis.

e18597 Background: TP53 mutations ( TP53 m) are uncommon in chronic-phase (CP) Philadelphia (Ph) chromosome–negative myeloproliferative neoplasms (MPN) but are increasingly reported in myelofibrosis (MF) and accelerated/blast phase (AP/BP). Their distribution, allelic configuration, and associated clinical outcomes have not been systematically synthesized. Methods: A PRISMA-guided search of EMBASE and PubMed (1974-July 1, 2025) identified cohort studies reporting adult Ph–negative MPNs with molecularly confirmed TP53 m. Case reports were excluded; Conference abstracts were included if cohort-level data were available. Extracted variables included demographics, MPN subtype, disease phase, TP53 allelic status (per International Consensus Classification), variant allele frequency (VAF), allogeneic hematopoietic cell transplantation (allo-HCT), median overall survival (mOS), and leukemic transformation. Given heterogeneity and lack of comparators, pooled proportions with (95% CI) were generated for descriptive variables; outcomes were summarized descriptively. Results: 10 retrospective studies met inclusion criteria. Pooled mean age was 61 years (95% CI 57.18–65.17) with male predominance (58%, 95 CI 53–63). TP53 m were uncommon in patients with Ph-negative MPN (3%, 95% CI 0–15%) but were higher in MF/AP/BP (10%, 95% CI 4–24%). Among patients with TP53 m, disease distribution included MF (35%, 95% CI 13–65%), AP/BP (33%, 95% CI 26–41%), essential thrombocythemia (ET) (10%, 95% CI 3–28%), and polycythemia vera (PV) (8%, 95% CI 4–14%). Multi-hit TP53 m accounted for 52% (95% CI 40–64%), while single-hit comprised 47% (95% CI 34–60%). The pooled mean TP53 VAF was 37.48% (95% CI 30.73–44.24%). Allo-HCT was used in 16% (95% CI 13–20%). One cohort reported leukemic transformation in 47% with a median follow-up of 9.6 months (m). Reported mOS in TP53 m CP-MF ranged from 11.6–18 m and was not reached in PV/ET, whereas AP/BP mOS ranged from 4.5–6 months. Conclusions: TP53 m Ph–negative MPNs are enriched in MF and AP/BP and frequently demonstrate multi-hit TP53 m with high VAF and associated with high leukemic transformation. Standardized molecular reporting and prospective studies are needed to refine prognostication and treatment strategies in TP53m MPN. Characteristics of patients with TP53 m MPN. Variable Pooled variables (95% CI) Age 61.18 years (57.18–65.17) Male/Female 58% (53–63)/42% (53–63) TP53 mutation in the cohort 3% (0–15) TP53 in MF/AP/BP 10% (CI 4–24) Primary myelofibrosis 35% (13–65) MPN in AP/BP 33% (26–41) Essential thrombocythemia 10% (CI 3–28) Polycythemia vera 8% (CI 4–14) Multi-hit/single-hit TP53 52% (CI 40–64) 47% (CI 34–60) TP53 VAF 37.48% (30.73–44.24) Abbreviations: MF: Myelofibrosis, AP: accelerated phase, BP: Blast phase, MPN: myeloproliferative neoplasm, VAF: Variant Allele Frequency.