The following is a summary of “Variation characteristics and clinical significance of TP53 in patients with myeloid neoplasms,” published in the August 2024 issue of Hematology by Ma et al.

Researchers conducted a retrospective study to investigate the hypothesis that while MDS and AML with TP53 variations generally have poor prognoses, specific TP53 variant types and variant allele frequencies (VAFs) may further differentiate patient outcomes.

They analyzed datasets of patients with MDS, MPN, and AML who had targeted DNA sequencing (February 2018 to December 2023), screening for patients with reportable TP53 variations. Demographic and clinical data were gathered, and the link between TP53 alterations and prognosis (AML/MDS) was examined using cBioPortal and Kaplan–Meier Plotter databases. Relationships between VAFs of TP53 variations and patient outcomes were analyzed using current study data.

The results showed 62 TP53 variants in 58 patients, with single mutations (79.31%, 46/58) being the most common, followed by double (17.24%, 10/58) and triple (3.45%, 2/58) mutations. Variations were mainly found in exon4–exon8 of TP53, with missense mutations (72.58%, 45/62) as the predominant type, followed by splice-site (9.68%, 6/62), nonsense (9.68%, 6/62), frameshift (6.45%, 4/62), and indel (1.61%, 1/62) mutations. High-frequency TP53 mutations included p.Arg175His and p.Arg273His, and common co-mutated genes were DNMT3A and TET2 in the three myeloid neoplasms. Some new TP53 variants in MPN were reported but were not previously found in public databases. Additionally, MDS or AML with TP53 alterations had a shorter OS compared to the unaltered group (P<0.01), and low TP53 mRNA levels correlated with shorter OS in patients with AML (P<0.01). Higher VAF (≥10%) was linked to shorter OS in patients with MDS (median 2.75 vs. 24 months) (P<0.01).

Investigators concluded that TP53 mutations primarily affected exons 4-8, were predominantly missense and single-nucleotide variants in myeloid neoplasms, and were associated with poor MDS/AML prognosis, with higher VAFs (≥10%) linked to shorter overall survival in patients with MDS.

Source: tandfonline.com/doi/full/10.1080/16078454.2024.2387878#abstract