1. TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups
- Author
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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, and Bejar, Rafael
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Hematology ,Genetics ,Rare Diseases ,Aged ,Aged ,80 and over ,Biomarkers ,Tumor ,Chromosome Aberrations ,Combined Modality Therapy ,Female ,Follow-Up Studies ,Humans ,Karyotyping ,Male ,Middle Aged ,Mutation ,Myelodysplastic Syndromes ,Prognosis ,Survival Rate ,Tumor Suppressor Protein p53 ,International Working Group for MDS Molecular Prognostic Committee ,Clinical Sciences ,Immunology ,Cardiovascular medicine and haematology ,Clinical sciences ,Oncology and carcinogenesis - 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.
- Published
- 2019