Abstract
Mutations of the TP53 gene occur in a subset of patients with acute myeloid leukemia (AML) and confer an exceedingly adverse prognosis. However, whether different types of TP53 mutations exert a uniformly poor outcome has not been investigated yet. Here, we addressed this issue by analyzing data of 1537 patients intensively treated within protocols of the German-Austrian AML study group. We classified TP53 mutations depending on their impact on protein structure and according to the evolutionary action (EAp53) score and the relative fitness score (RFS). In 98/1537 (6.4%) patients, 108 TP53 mutations were detected. While the discrimination depending on the protein structure and the EAp53 score did not show a survival difference, patients with low-risk and high-risk AML-specific RFS showed a different overall survival (OS; median, 12.9 versus 5.5 months, p = 0.017) and event-free survival (EFS; median, 7.3 versus 5.2 months, p = 0.054). In multivariable analyses adjusting for age, gender, white blood cell count, cytogenetic risk, type of AML, and TP53 variant allele frequency, these differences were statistically significant for both OS (HR, 2.14; 95% CI, 1.15–4.0; p = 0.017) and EFS (HR, 1.97; 95% CI, 1.06–3.69; p = 0.033). We conclude that the AML-specific RFS is of prognostic value in patients with TP53-mutated AML and a useful tool for therapeutic decision-making.
Highlights
Acute myeloid leukemia (AML) is a heterogeneous aggressive malignancy occurring de novo, secondary to antecedent hematological disorders, or following cytotoxic treatments for a primary disease [1,2,3,4]
We described deleterious germline tumor protein p53 (TP53) mutations in patients with acute myeloid leukemia (AML), preferably in therapy-related subtypes developing after ionizing irradiation [33,34]
We investigated the prognostic impact of different TP53 mutations using four TP53-specific functional scoring systems in a large cohort of intensively treated patients of the German-Austrian AML study group (AMLSG)
Summary
Acute myeloid leukemia (AML) is a heterogeneous aggressive malignancy occurring de novo, secondary to antecedent hematological disorders, or following cytotoxic treatments for a primary disease [1,2,3,4]. It is the most common acute leukemia in adults with an annual age-adjusted incidence rate of 3.5/100,000 men and women rising to 15–20/100,000 above the age of 60 years [5]. While preLSCs do not generate leukemia in vivo, leukemic stem cells (LSCs) representing a distinct population with self-renewal capacity are capable to induce and perpetuate leukemia [13]. In the vast majority of AMLs, multiple and diverse genetic subclones are observed [14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
