Are TP53 mutations all alike?
Open accessAbstract
TP53 is mutated in 10 to 15% of cases of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and is associated with a previous exposure to cytotoxic therapy, complex cytogenetic abnormalities, and a poor prognosis. Recent data have established the importance of TP53-mutant allele status, the determination of which requires specific genetic testing. Compared with monoallelic disease, multihit TP53-mutant AML/MDS is associated with chromosomal abnormalities and decreased overall survival. Most TP53 mutations are missense mutations that localize to the DNA binding domain. Hot-spot mutations involving residues R175, Y220, G245, R248, R273, or R282 represent approximately 35% of all TP53 missense mutations in AML/MDS. There is evidence that these hot-spot mutations may have dominant negative or gain-of-function properties. Here we review this evidence and discuss its potential impact on patient outcomes and clinical management.
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A recent study identified 92% of TP53 mutant MDS/AML patients to represent a poor risk population.
“with a recent study identifying 92% of TP53 mutant MDS/AML patients to represent a poor risk population.”
From Long‐term follow‐up and combined Phase 2 results of eprenetapopt and azacitidine in patients with <i>TP53</i> mutant MDS/AML (2025) · cites this paper as [11]
In Clinical Case 1 (page not specified), the paper reports multihit TP53 involvement in 40 of 41 AML/MDS cases, labels this 91%, and describes multihit disease as indicating a dismal prognosis. It does not report the claimed 92%; moreover, 40 of 41 does not calculate to 91%, so the paper’s own figures are inconsistent. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThere is a strong interplay between VAF, allelic state, and cytogenetic complexity predicting outcomes in mTP53 MDS/AML.
“there is a very strong interplay between VAF, allelic state, and cytogenetic complexity strongly predicting outcomes in this molecular subset”
From Long‐term follow‐up and combined Phase 2 results of eprenetapopt and azacitidine in patients with <i>TP53</i> mutant MDS/AML (2025) · cites this paper as [11]
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References 35 · Cited by 11
Research works printed but not linked: 29
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- Authors
- Wong, T. N., & Link, D. C.
- Affiliations
- University of Michigan (US)
- Washington University in St. Louis (US)
- Corresponding author
- Link, Daniel C.
- Venue
- Hematology
- Publisher
- American Society of Hematology
- Published
- 2024-12-06
- Volume
- 2024
- Issue
- 1
- Pages
- 321-325
- ISSN
- 1520-4383 (ISSN-L)
- 1520-4391
- PMC
- PMC11665718
- OpenAlex
- W4405109155
- Cited by
- 11
- References
- 35
- Citations by year
- 2026: 4 · 2025: 7
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hematology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- TP53 mutation, acute myeloid leukemia, myelodysplastic syndrome, hot spot mutations, missense mutations, DNA-binding domain, dominant negative effect, chromosomal abnormalities, prognosis, overall survival
- MeSH terms
- Chromosome Aberrations, Humans, Mutation, Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Tumor Suppressor Protein p53, Mutation, Missense
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