Clinical Characteristics, Co-Mutations, and Prognostic Factors of TP53 Mutations in Acute Myeloid Leukemia and Myelodysplastic Syndrome.

BACKGROUND

TP53 mutations confer poor prognosis and heterogeneous clinical features in myeloid neoplasms, but distinguishing factors between AML and MDS and independent prognostic markers within this high-risk group remain unclear.

METHODS

This retrospective study evaluated 45 adult patients with TP53-mutated acute myeloid leukemia (AML; n = 22) or myelodysplastic syndromes (MDS; n = 23) treated at Ganzhou People's Hospital between 2018 and 2023. Clinical, laboratory, cytogenetic, and targeted next-generation sequencing data were collected at diagnosis. Sixteen genes frequently mutated in myeloid malignancies were assessed for co-mutation patterns. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier and Cox regression; variables with univariate p < 0.10 entered multivariate models.

RESULTS

MDS patients were older than AML patients (65.5 ± 9.0 vs. 56.0 ± 15.1 years; p = 0.013), and exhibited lower bone marrow blast percentages (5.6% vs. 49.5%; p < 0.001), while AML cases had higher peripheral WBC counts (8.6 × 10⁹ vs. 2.9 × 10⁹/L; p = 0.002). DNMT3A and TET2 co-mutations were most frequent (15.6% each); FLT3-ITD was enriched in AML (18.2% vs. 0%; p = 0.049). In multivariate analysis, allogeneic HSCT (HR = 0.08; p = 0.022), higher RBC count (HR = 0.39; p = 0.011), hemoglobin (HR = 0.98; p = 0.043), and albumin (HR = 0.91; p = 0.010) independently predicted superior PFS, whereas RUNX1 co-mutation (HR = 18.15; p = 0.028) and lower ALT (HR = 0.97; p = 0.018) were independently associated with OS.

CONCLUSIONS

Distinct clinical and molecular features differentiate TP53-mutated AML from MDS. Allogeneic HSCT confers marked survival benefit, and RUNX1 co-mutation identifies an ultra-high-risk subset. Early trans-plant evaluation combined with comprehensive genomic profiling is recommended to guide personalized treatment in this high-risk population.