Influence of TP53 gene mutations and their allelic status in myelodysplastic syndromes with isolated 5q deletion.
Journal
Blood
Journal Volume
144
Journal Issue
16
Start Page
1722
End Page
1731
ISSN
1528-0020
Date Issued
2024-10-17
Author(s)
Montoro, Maria Julia
Palomo, Laura
Haferlach, Claudia
Acha, Pamela
Chan, Onyee
Navarro, Víctor
Kubota, Yasuo
Schulz, Felicitas Isabel
Meggendorfer, Manja
Briski, Robert
Al Ali, Najla
Xicoy, Blanca
López-Cadenas, Félix
Bosch, Francesc
González, Teresa
Eder, Lea Naomi
Jerez, Andrés
Wang, Yu-Hung
Campagna, Alessia
Santini, Valeria
Bernal Del Castillo, Teresa
Such, Esperanza
Diaz Varela, Nicolás
Platzbecker, Uwe
Haase, Detlef
Díez-Campelo, María
Della Porta, Matteo
Garcia-Manero, Guillermo
Wiseman, Daniel H
Germing, Ulrich
Maciejewski, Jaroslaw P
Komrokji, Rami S
Sole, Francesc
Haferlach, Torsten
Valcárcel, David
Abstract
Mutations in the TP53 gene, particularly multihit alterations, have been associated with unfavorable clinical features and prognosis in patients diagnosed with myelodysplastic syndrome (MDS). Despite this, the role of TP53 gene aberrations in MDS with isolated deletion of chromosome 5 [MDS-del(5q)] remains unclear. This study aimed to assess the impact of TP53 gene mutations and their allelic state in patients with MDS-del(5q). To that end, a comprehensive analysis of TP53 abnormalities, examining both TP53 mutations and allelic imbalances, in 682 patients diagnosed with MDS-del(5q) was conducted. Twenty-four percent of TP53-mutated patients exhibited multihit alterations, whereas the remaining patients displayed monoallelic mutations. TP53-multihit alterations were predictive of an increased risk of leukemic transformation. The impact of monoallelic alterations was dependent on the variant allele frequency (VAF); patients with TP53-monoallelic mutations and VAF <20% exhibited behavior similar to TP53 wild type, and those with TP53-monoallelic mutations and VAF ≥20% presented outcomes equivalent to TP53-multihit patients. This study underscores the importance of considering TP53 allelic state and VAF in the risk stratification and treatment decision-making process for patients with MDS-del(5q).
Type
journal article