TP53 in Acute Myeloid Leukemia: Molecular Aspects and Patterns of Mutation
Abstract
:1. Introduction
2. TP53 Gene, p53 Structure and Cellular Functions
3. Role of TP53 in Hematopoiesis, Clonal Hematopoiesis and AML
4. Functional Patterns of TP53 Mutations
4.1. Amino Terminal Domain Mutants (AT)
4.2. DNA Binding Domain (DBD)
4.3. Oligomerization Domain (OD)
5. Co-occurring Mutations and Allelic States in TP53 AML
6. Current Standard Therapeutic Concepts
7. Newer Molecularly Targeted Therapies
7.1. Mutant TP53 Inhibitor-APR-456
7.2. MDM2 Inhibitors
7.3. Immunotherapy and Other Agents
8. Conclusions
Funding
Conflicts of Interest
References
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Target | Clinical Trial Number | Antineoplastic Combination | Compound | Phase (Status) |
---|---|---|---|---|
MDM2 | NCT01773408 | ARA-C | Idasanutlin/Cometinib | I/IB (Completed) |
NCT02098967 | Alone or AZA | Milademetan | I (Completed) | |
NCT02545283 | ARA-C | AMG-232 | III (Recruiting) | |
NCT03671564 | DAC | HDM201 | I (Recruiting) | |
NCT02319369 | Alone or AZA | DS-3032b/Milademetan | I (Recruiting) | |
NCT03634228 | Ara-Ca | I/II (Recruiting) | ||
NCT03041688 | DAC | AMG-232 | IB (Recruiting) | |
NCT02143635 | HDM201 | I (Recruiting) | ||
MDM2 & BCL2 | NCT02670044 | Dasanutlin/VEN | IB/II (Recruiting) | |
MDM2 & MDMX | NCT02909972 | Alone or AZA | ALRN-6924 | I (Recruiting) |
Target | Clinical Trial Number | Antineoplastic Combination | Compound | Phase (Status) |
---|---|---|---|---|
Mutant TP53 | NCT03072043 | AZA | APR-246/PRIMA-1Met | IB/II (Recruiting) |
Several targets | NCT03381781 | DAC | Arsenic Trioxide | II (Recruiting) |
HMG-CoAreductase | NCT03560882 | Atorvastatin/Lipitor | I (Recruiting) |
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George, B.; Kantarjian, H.; Baran, N.; Krocker, J.D.; Rios, A. TP53 in Acute Myeloid Leukemia: Molecular Aspects and Patterns of Mutation. Int. J. Mol. Sci. 2021, 22, 10782. https://doi.org/10.3390/ijms221910782
George B, Kantarjian H, Baran N, Krocker JD, Rios A. TP53 in Acute Myeloid Leukemia: Molecular Aspects and Patterns of Mutation. International Journal of Molecular Sciences. 2021; 22(19):10782. https://doi.org/10.3390/ijms221910782
Chicago/Turabian StyleGeorge, Binsah, Hagop Kantarjian, Natalia Baran, Joseph Douglas Krocker, and Adan Rios. 2021. "TP53 in Acute Myeloid Leukemia: Molecular Aspects and Patterns of Mutation" International Journal of Molecular Sciences 22, no. 19: 10782. https://doi.org/10.3390/ijms221910782