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Mutational analysis of therapy-related myelodysplastic syndromes and acute myelogenous leukemia
Open accessAbstract
Therapy-related myelodysplastic syndromes and acute myelogenous leukemia comprise a poor-risk subset of myelodysplastic syndromes and acute myelogenous leukemia. Large-scale mutation profiling efforts in de novo myelodysplastic syndromes have identified mutations that correlate with clinical features, but such mutations have not been investigated in therapy-related myelodysplastic syndromes and acute myelogenous leukemia. Genomic DNA from 38 patient samples were subjected to high throughput polymerase chain reaction and sequenced for TP53, TET2, DNMT3A, ASXL1, IDH1, IDH2, EZH2, EED, SUZ12, RBBP4, SRSF2, U2AF35, and SF3B1. We identified somatic mutations in 16 of 38 (42%) patients. TP53 mutations were the most common lesion, detected in 8 of 38 (21%) patients, followed by TET2 in 4 of 38 (10.5%). Cases with a TP53 mutation or loss of the TP53 locus had a worse overall survival compared to those with wild-type TP53 (8.8 vs. 37.4 months; P=0.0035).
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“There are several features that distinguish t-AML from de novo AML including a higher incidence of TP53 mutations2,3, abnormalities of chromosomes 5 or 7, complex cytogenetics, and a reduced response to chemotherapy4.”
From Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia (2015) · cites this paper as [3]
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Metadata
- Authors
- Shih, A. H., Chung, S. S., Dolezal, E. K., Zhang, S.-J., Abdel-Wahab, O. I., Park, C. Y., Nimer, S. D., Levine, R. L., & Klimek, V. M.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Venue
- Haematologica
- Published
- 2013-01-24
- Volume
- 98
- Issue
- 6
- Pages
- 908-912
- ISSN
- 0390-6078 (ISSN-L)
- 1592-8721
- PMC
- PMC3669447
- OpenAlex
- W2169313200
- Cited by
- 135
- References
- 31
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 8 · 2021: 9 · 2020: 15 · 2019: 13 · 2018: 11 · 2017: 14 · 2016: 12 · 2015: 9 · 2014: 14 · 2013: 4
- FWCI
- 9.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Haematologica (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Dana Foundation
- American Society of Hematology
- Leukemia and Lymphoma Society
- Memorial Sloan-Kettering Cancer Center
- National Institutes of Health
- National Cancer Institute (R01CA138234, U54CA143798, P30CA008748)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
- Keywords
- therapy-related myelodysplastic syndrome, somatic mutations, TP53 mutation, TET2, DNMT3A, ASXL1, IDH1, IDH2, EZH2, SUZ12, RBBP4, SRSF2, U2AF35, SF3B1, p53 deficiency, overall survival, prognostic factors
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, DNA Mutational Analysis, Female, Humans, Male, Middle Aged, Mutation, Myelodysplastic Syndromes, Prognosis, Radiotherapy, Leukemia, Myeloid, Acute, Tumor Suppressor Protein p53, Mutation Rate
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