Abstract 5302: Defining the landscape of TP53 mutations in acute myeloid leukemia

Abstract Background and Objective: The TP53 gene is one of the most frequently mutated genes in human cancers. TP53 mutations can be classified as functional, partially functional, or nonfunctional. In gynecologic cancers, this information has been used to identify patients who are sensitive to bevacizumab and has led to the exploration across multiple cancer types of “p53 reactivators” to restore normal p53 activity. In myeloid neoplasms, the 10 most commonly mutated amino acid residues account for 30% of all TP53 mutations, all located within the DNA-binding domain. However, protein functionality has not been sufficiently described in the context of acute myeloid leukemia (AML). The main goal of this study is to analyze the functional classification of TP53 mutations in AML. Methods: TP53-mutated AML cases were identified by searching for “TP53” in next-generation sequencing reports within TriCore Reference Laboratories’ laboratory information system. Cases were individually reviewed to include those with an AML diagnosis (n=76) and those treated at the University of New Mexico (UNM) (n=12). Molecular, cytogenetic, histologic findings, laboratory values, and clinical data were collected and recorded in REDCap, a secure translational research database. The National Cancer Institute’s TP53 Database was used to classify TP53 mutations and assign functional classifications. Results: Of the 76 patients, 43 had a single TP53 mutation and 21 had two or more TP53 mutations. A total of 89 TP53 mutations were identified, including 68 non-functional mutations, five partially functional mutations, one functional mutation, and 15 unclassified mutations. Twelve patients (12/76) received treatment at UNM and had additional cytogenetic and prognostic data. Seven patients (7/12) had a complex karyotype, and six patients (6/12) had chromosome 17 alterations at diagnosis. 11 patients (11/12) had non-functional or unclassified TP53 mutations. These patients had a median overall survival of 6.4 months. A single patient (1/12) was found to have a functional TP53 mutation and is currently alive 17.6 months after diagnosis. Conclusion: Our findings indicate that a majority of patients diagnosed with TP53-mutated AML have non-functional mutations. However, a single patient with a functional TP53 mutation showed a significantly better clinical course. Further subclassification of TP53 mutation functionality may be necessary for accurate prognosis predictions and for novel therapeutic approaches. Citation Format: Joseph Stenberg, Jordan Redemann, Jessica Lewis-Gonzalez, Rama Gullapalli, Charles Foucar. Defining the landscape of TP53 mutations in acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5302.