Version 1
: Received: 12 September 2023 / Approved: 13 September 2023 / Online: 13 September 2023 (10:09:18 CEST)
How to cite:
Zawacka, J. p53 Biology and Reactivation for Improved Therapy in MDS and AML–Are We Building Castles in the Air?. Preprints2023, 2023090848. https://doi.org/10.20944/preprints202309.0848.v1
Zawacka, J. p53 Biology and Reactivation for Improved Therapy in MDS and AML–Are We Building Castles in the Air?. Preprints 2023, 2023090848. https://doi.org/10.20944/preprints202309.0848.v1
Zawacka, J. p53 Biology and Reactivation for Improved Therapy in MDS and AML–Are We Building Castles in the Air?. Preprints2023, 2023090848. https://doi.org/10.20944/preprints202309.0848.v1
APA Style
Zawacka, J. (2023). p53 Biology and Reactivation for Improved Therapy in MDS and AML–Are We Building Castles in the Air?. Preprints. https://doi.org/10.20944/preprints202309.0848.v1
Chicago/Turabian Style
Zawacka, J. 2023 "p53 Biology and Reactivation for Improved Therapy in MDS and AML–Are We Building Castles in the Air?" Preprints. https://doi.org/10.20944/preprints202309.0848.v1
Abstract
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) originate from preleukemic hematopoietic conditions, such as clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenia of undetermined significance (CCUS) and have desolate outcomes. The prognosis is worse in patients with TP53 mutations which are often linked to complex karyotypes and contribute to worse responses to induction therapy, demethylating agents or venetoclax-based treatments. Survival of patients with TP53 gene mutations is often less than one year. Therefore, TP53-mutated MDS and AML are now classified separately in the unfavorable risk category. In the clinical setting, the wild-type p53 is reactivated pharmacologically by targeting p53/MDM2/MDM4 interactions and mutant p53 reactivation is achieved by refolding the DNA binding domain to wild-type-like conformation or via targeted degradation of the mutated protein. This review discusses our current understanding of p53 biology in MDS and AML and the promises and failures of p53 reactivation in the clinical trial setting.
Keywords
MDS; AML; p53; MDM2; MDM4; p73; improved therapy
Subject
Medicine and Pharmacology, Hematology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
