Revised diagnostic criteria for myeloid neoplasms (MN) issued by the International Consensus Classification (ICC) and the World Health Organization (WHO) recommended major change pertaining to TP53-mutated (TP53mut) MN. However, these assertions have not been specifically examined in therapy-related myeloid neoplasm (t-MN), a subset enriched with TP53mut. We analyzed 488 t-MN patients for TP53mut. At least one TP53mut with variant allele frequency (VAF) ≥ 2% with or without loss of TP53 locus was noted in 182 (37.3%) patients and 88.2% of TP53mut t-MN had a VAF ≥10%. TP53mut t-MN with VAF ≥ 10% had a distinct clinical and biological profile compared to both TP53mut VAF < 10% and wild-type TP53 (TP53wt) cases. Notably, TP53mut VAF ≥ 10% had a significantly shorter survival compared to TP53wt (8.3 vs. 21.6 months; P < 0.001), while the survival of TP53mut VAF < 10% was comparable to TP53wt. Within TP53mut VAF ≥ 10% cohort, the inferior outcomes persisted irrespective of the single- or multi-hit status, co-mutation pattern, or treatments received. Finally, survival of TP53mut patients was poor across all the blast categories and MDS patients with >10% blasts had inferior survival compared to <5%. In summary, TP53mut VAF ≥10% signified a clinically and molecularly homogenous cohort regardless of the allelic status.
国际共识分类（ICC）与世界卫生组织（WHO）发布的修订版髓系肿瘤（MN）诊断标准中，针对TP53突变（TP53mut）型MN提出了重要变更建议。然而，这些观点尚未在富含TP53mut的特定亚群——治疗相关髓系肿瘤（t-MN）中得到专门验证。我们对488例t-MN患者进行了TP53突变分析，其中182例（37.3%）患者检出至少一种变异等位基因频率（VAF）≥2%的TP53突变（伴或不伴TP53基因位点缺失），且88.2%的TP53mut型t-MN患者VAF≥10%。与TP53mut VAF<10%及TP53野生型（TP53wt）病例相比，VAF≥10%的TP53mut型t-MN展现出独特的临床与生物学特征。值得注意的是，TP53mut VAF≥10%患者的中位生存期较TP53wt患者显著缩短（8.3个月 vs 21.6个月；P<0.001），而TP53mut VAF<10%患者的生存情况与TP53wt患者相当。在TP53mut VAF≥10%群体中，无论单等位基因或多等位基因突变状态、共突变模式或接受的治疗方案如何，其不良预后均持续存在。最后，在所有原始细胞比例分级中，TP53mut患者均表现较差生存结局，且原始细胞>10%的MDS患者生存期显著低于原始细胞<5%者。综上所述，TP53mut VAF≥10%标志着具有临床与分子同质性的患者群体，且该特征不受等位基因状态影响。
肿瘤(癌症)患者之家