학술논문
TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups.
Document Type
article
Author
Haase, Detlef; Stevenson, Kristen E; Neuberg, Donna; Maciejewski, Jaroslaw P; Nazha, Aziz; Sekeres, Mikkael A; Ebert, Benjamin L; Garcia-Manero, Guillermo; Haferlach, Claudia; Haferlach, Torsten; Kern, Wolfgang; Ogawa, Seishi; Nagata, Yasunobu; Yoshida, Kenichi; Graubert, Timothy A; Walter, Matthew J; List, Alan F; Komrokji, Rami S; Padron, Eric; Sallman, David; Papaemmanuil, Elli; Campbell, Peter J; Savona, Michael R; Seegmiller, Adam; Adès, Lionel; Fenaux, Pierre; Shih, Lee-Yung; Bowen, David; Groves, Michael J; Tauro, Sudhir; Fontenay, Michaela; Kosmider, Olivier; Bar-Natan, Michal; Steensma, David; Stone, Richard; Heuser, Michael; Thol, Felicitas; Cazzola, Mario; Malcovati, Luca; Karsan, Aly; Ganster, Christina; Hellström-Lindberg, Eva; Boultwood, Jacqueline; Pellagatti, Andrea; Santini, Valeria; Quek, Lynn; Vyas, Paresh; Tüchler, Heinz; Greenberg, Peter L; Bejar, Rafael; International Working Group for MDS Molecular Prognostic Committee
Source
Leukemia. 33(7)
Subject
Language
Abstract
Risk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnormalities and somatic mutations. To refine risk stratification of CK-MDS patients, we examined data from 359 CK-MDS patients shared by the International Working Group for MDS. Mutations were underrepresented with the exception of TP53 mutations, identified in 55% of patients. TP53 mutated patients had even fewer co-mutated genes but were enriched for the del(5q) chromosomal abnormality (p 10%), abnormal 3q, abnormal 9, and monosomy 7 as having the greatest survival risk. The poor risk associated with CK-MDS is driven by its association with prognostically adverse TP53 mutations and can be refined by considering clinical and karyotype features.