TP53 Alterations in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Ramy Rahmé, Thorsten Braun, James J. Manfredi, Pierre Fenaux

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Article number1152
Issue number4
StatePublished - Apr 2023


  • acute myeloid leukemia
  • cancer
  • mutant p53
  • myelodysplasia


Dive into the research topics of 'TP53 Alterations in Myelodysplastic Syndromes and Acute Myeloid Leukemia'. Together they form a unique fingerprint.

Cite this