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Current status and new treatment approaches in TP53 mutated AML
Abstract
Mutations in the essential tumor suppressor gene, TP53, are observed in only 5-10% of acute myeloid leukemia (AML) cases, but are highly associated with therapy-related AML and cases with complex karyotype. The mutational status of TP53 is a critical prognostic indicator, with dismal outcomes consistently observed across studies. Response rates to traditional cytotoxic chemotherapy are poor and long-term survival after allogeneic hematopoietic stem cell transplant is rare. Therapy with hypomethylating agents has resulted in a modest improvement in outcomes over intensive chemotherapy, but durable responses are seldom observed. In view of the intrinsic resistance to standard chemotherapies conferred by mutations in TP53, novel treatment approaches are required. In this review, we examine the current treatment landscape in TP53 mutated AML and discuss emerging therapeutic approaches currently under clinical investigation.
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“TP53 gene mutations are detected in approximately 10%-20% of patients with de novo myelodysplastic syndromes (MDS)1-4 or acute myeloid leukemia (AML)5,6 and 30%-40% of patients with therapy-related disease.7”
From Eprenetapopt (APR-246) and Azacitidine in TP53 -Mutant Myelodysplastic Syndromes (2021) · cites this paper as [6]
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Daver, N. G., Iqbal, S., Renard, C., Chan, R. J., Hasegawa, K., Hu, H., Tse, P., Yan, J., Zoratti, M. J., Xie, F., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22617338
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Metadata
- Authors
- Hunter, A. M., & Sallman, D. A.
- Affiliations
- University of South Florida (US)
- Moffitt Cancer Center (US)
- Corresponding author
- Sallman, David A.
- Venue
- Best Practice & Research Clinical Haematology
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 32
- Issue
- 2
- Pages
- 134-144
- ISSN
- 1521-6926 (ISSN-L)
- OpenAlex
- W2944248311
- Cited by
- 102
- References
- 132
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 11 · 2023: 20 · 2022: 19 · 2021: 26 · 2020: 10 · 2019: 2
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Best Practice & Research Clinical Haematology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Celgene
- Jazz
- 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 › Oncology › Cancer-related Molecular Pathways
- Keywords
- TP53 mutation, acute myeloid leukemia, therapy-related AML, complex karyotype, prognostic factors, chemoresistance, hypomethylating agents, allogeneic hematopoietic stem cell transplantation, novel therapeutic approaches, targeted therapy
- MeSH terms
- Humans, Mutation, Time Factors, Leukemia, Myeloid, Acute, Survival Rate, Tumor Suppressor Protein p53, Disease-Free Survival
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