Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 18, Pages -Publisher
MDPI
DOI: 10.3390/ijms221810105
Keywords
MDS; AML; TP53; magrolimab; eprenetapopt
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This article reviews the progress in targeting TP53 mutated myelodysplastic syndromes and acute myeloid leukemia, focusing on the use of active agents and future treatment directions. It emphasizes the importance of understanding the clinical characteristics of the disease and the impact of TP53 mutant burden on patient clinical trajectory.
Targeting TP53 mutated myelodysplastic syndromes and acute myeloid leukemia remains a significant unmet need. Recently, new drugs have attempted to improve the outcomes of this poor molecular subgroup. The aim of this article is to review all the current knowledge using active agents including hypomethylating agents with venetoclax, eprenetapopt or magrolimab. We include comprehensive analysis of clinical trials to date evaluating these drugs in TP53 myeloid neoplasms as well as discuss future novel combinations for consideration. Additionally, further understanding of the unique clinicopathologic components of TP53 mutant myeloid neoplasms versus wild-type is critical to guide future study. Importantly, the clinical trajectory of patients is uniquely tied with the clonal burden of TP53, which enables serial TP53 variant allele frequency analysis to be a critical early biomarker in investigational studies. Together, significant optimism is now possible for improving outcomes in this patient population.
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