Year: 2023
Type: review
Abstract: TP53 mutations are less frequent in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) than in solid tumors, except in secondary and therapy-related MDS/AMLs, and in cases with complex monosomal karyotype. As in solid tumors, missense mutations predominate, with the same hotspot mutated codons (particularly codons 175, 248, 273). As TP53-mutated MDS/AMLs are generally associated with complex chromosomal abnormalities, it is not always clear when TP53 mutations occur in the pathophysiological process. It is also uncertain in these MDS/AML cases, which often have inactivation of both TP53 alleles, if the missense mutation is only deleterious through the absence of a functional p53 protein, or through a potential dominant-negative effect, or finally a gain-of-function effect of mutant p53, as demonstrated in some solid tumors. Understanding when TP53 mutations occur in the disease course and how they are deleterious would help to design new treatments for those patients who generally show poor response to all therapeutic approaches.
Source: Biomedicines
Institutions: Inserm, Université Paris Cité, Université Sorbonne Paris Nord, Assistance Publique – Hôpitaux de Paris, Hôpital Avicenne, Tisch Cancer Institute, Institut de recherche Saint-Louis, Hématopoïèse normale et pathologique : Emergence, environnement et recherche translationnelle, Laboratoire d'hématologie, Icahn School of Medicine at Mount Sinai, Hôpital Saint-Louis
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,447
OpenAlex ID: W4365141968