Effect of Biallelic TP53 Mutations in Changing the Subclassification of Myelodysplastic Neoplasm

Background: TP53 mutation confers a poor prognosis in myelodysplastic neoplasms (MDS).A new subtype of MDS with biallelic TP53 inactivation (MDS-biTP53) was introduced in the 5th edition of the WHO classification.The goal of this study was to determine the impact of the new molecular based classification on the morphologic subtypes of MDS.Methods: Our Next Generation Sequencing (NGS) database from 2017-2023 yielded 49 cases of MDS with TP53 mutations.The cases were reclassified as MDS-biTP53 if they fulfilled the WHO criteria: variant allele frequency (VAF) of >49% for TP53 mutation, >1 mutation in the TP53 gene, or TP53 deletion by Fluorescent in-situ hybridization (FISH) with at least one TP53 mutation. Results:The distribution of 49 cases of MDS with TP53 mutations is listed in Table 1.Thirty-three cases were reclassified as MDS-biTP53 based on NGS data.Of these, 17 cases had TP53 mutation with a VAF of >49%, and 16 cases had two TP53 mutations.Five additional cases were reclassified as MDS-biTP53 based on combined NGS and FISH results.Out of 38 cases of MDS-biTP53, cytogenetic findings were available for 35 cases, 29 of which had complex karyotype.Four out of 11 cases of monoallelic TP53 mutation had complex cytogenetics (p-value 0.0058).The median overall survival (OS) was poor, at 13.8 months for MDS-biTP53 and 17.7 months for MDS with monoallelic TP53 mutation, but there was no significant difference between subgroups (p-value 0.12). Conclusion:Applying new molecular criteria for MDS subtyping resulted in the change of morphologic subclassification in 77% of the cases.Complex cytogenetics was significantly associated with MDS-biTP53.