The World Health Organization (WHO-5) and International Consensus Classification (ICC) acknowledge the poor prognosis of TP53-mutated (TP53mut) myeloid neoplasm (MN). However, there are substantial differences between the two classifications that may lead to under- or overestimation of the prognostic risk. We retrospectively applied WHO-5 and ICC to 603 MN cases harboring TP53mut (variant allele frequency, VAF ≥ 2%). WHO-5 and ICC would not classify 64% and 20% of these cases as TP53mut MN, respectively. Moreover, of those classified, 67.5% would be classified discrepantly. Primary drivers of discrepancies included: (i) prognostic importance of TP53mut acute myeloid leukemia (AML), (ii) interaction of the blast percentage and allelic status, (iii) 17p.13.1 deletion detected by cytogenetics, (iv) complex karyotype (CK) as multi-hit equivalent, and (v) TP53mut VAF threshold, we analyzed survival outcomes of each of these groups with an aim to provide clarity. TP53mut AML was associated with significantly poor survival compared to TP53-wild type TP53wt AML, myelodysplasia-related (AML, MR 4.7 vs. 18.3 months; P < 0.0001), supporting its inclusion within TP53mut MN as a distinct subentity. Secondly, the survival of TP53mut with blast 10–19% was poor regardless of the allelic status. Thirdly, for cases with a single TP53mut with VAF < 50%, 17p13.1 del or CK serve as practical surrogates of biallelic inactivation, obviating the need for an additional copy number analysis. Finally, TP53mut AML, MDS multi-hit/multi-hit equivalent with VAF < 10% had significantly poorer survival compared to TP53mut MDS VAF < 10% without CK and 17p del, and were comparable to those with VAF ≥ 10% (14.1 vs. 48.8 vs.7.8 months, P < 0.0001). Collectively, these findings address key areas of contention and provide valuable insights that will guide future revisions of the WHO and ICC classifications.
世界卫生组织（WHO-5）与国际共识分类（ICC）均承认TP53突变（TP53mut）髓系肿瘤（MN）预后不良，但两种分类体系存在显著差异，可能导致预后风险的低估或高估。我们回顾性应用WHO-5和ICC标准对603例携带TP53mut（变异等位基因频率≥2%）的MN病例进行分析。结果显示，分别有64%和20%的病例未被WHO-5和ICC归类为TP53mut MN。此外，在已分类病例中，67.5%存在分类不一致现象。差异主要源于以下因素：（1）TP53mut急性髓系白血病（AML）的预后重要性；（2）原始细胞比例与等位状态的交互影响；（3）细胞遗传学检测到的17p13.1缺失；（4）复杂核型作为多打击等效标志；（5）TP53mut VAF阈值。我们通过分析各亚组生存结局以明确其临床意义。与TP53野生型AML相比，TP53mut AML（包括骨髓增生异常相关AML）生存期显著缩短（4.7个月 vs 18.3个月，P<0.0001），支持将其作为独立亚类纳入TP53mut MN范畴。其次，原始细胞比例10-19%的TP53mut病例无论等位状态如何均预后不良。第三，对于VAF<50%的单等位TP53mut病例，17p13.1缺失或复杂核型可作为双等位失活的实用替代指标，无需额外进行拷贝数分析。最后，在VAF<10%的病例中，伴复杂核型或17p缺失的TP53mut AML、多打击/多打击等效MDS患者生存期（14.1个月）显著低于不伴复杂核型与17p缺失的TP53mut MDS患者（48.8个月），而与VAF≥10%患者（7.8个月）具有可比性（P<0.0001）。这些发现系统解析了分类争议的关键环节，为未来WHO与ICC分类修订提供了重要依据。
肿瘤(癌症)患者之家