TY - JOUR
T1 - Are TP53 mutations all alike?
AU - Wong, Terrence N.
AU - Link, Daniel C.
N1 - Publisher Copyright:
Copyright © 2024 by The American Society of Hematology.
PY - 2024/11/25
Y1 - 2024/11/25
N2 - TP53 is mutated in 10 to 15% of cases of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and is associated with a previous exposure to cytotoxic therapy, complex cytogenetic abnormalities, and a poor prognosis. Recent data have established the importance of TP53-mutant allele status, the determination of which requires specific genetic testing. Compared with monoallelic disease, multihit TP53-mutant AML/MDS is associated with chromosomal abnormalities and decreased overall survival. Most TP53 mutations are missense mutations that localize to the DNA binding domain. Hot-spot mutations involving residues R175, Y220, G245, R248, R273, or R282 represent approximately 35% of all TP53 missense mutations in AML/MDS. There is evidence that these hot-spot mutations may have dominant negative or gain-of-function properties. Here we review this evidence and discuss its potential impact on patient outcomes and clinical management.
AB - TP53 is mutated in 10 to 15% of cases of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and is associated with a previous exposure to cytotoxic therapy, complex cytogenetic abnormalities, and a poor prognosis. Recent data have established the importance of TP53-mutant allele status, the determination of which requires specific genetic testing. Compared with monoallelic disease, multihit TP53-mutant AML/MDS is associated with chromosomal abnormalities and decreased overall survival. Most TP53 mutations are missense mutations that localize to the DNA binding domain. Hot-spot mutations involving residues R175, Y220, G245, R248, R273, or R282 represent approximately 35% of all TP53 missense mutations in AML/MDS. There is evidence that these hot-spot mutations may have dominant negative or gain-of-function properties. Here we review this evidence and discuss its potential impact on patient outcomes and clinical management.
UR - http://www.scopus.com/inward/record.url?scp=85212018541&partnerID=8YFLogxK
U2 - 10.1182/hematology.2024000556
DO - 10.1182/hematology.2024000556
M3 - Review article
C2 - 39644062
AN - SCOPUS:85212018541
SN - 1520-4391
VL - 2024
SP - 321
EP - 325
JO - Hematology. American Society of Hematology. Education Program
JF - Hematology. American Society of Hematology. Education Program
IS - 1
ER -