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| Leukemia. 2019 Jan 11. doi: 10.1038/s41375-018-0351-2. pii: 10.1038/s41375-018-0351-2 |
| TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups. |
| Haase D1, Stevenson KE2, Neuberg D3, Maciejewski JP4, Nazha A5, Sekeres MA6, Ebert BL7, Garcia-Manero G8, Haferlach C9, Haferlach T10, Kern W11, Ogawa S12, Nagata Y13, Yoshida K14, Graubert TA15, Walter MJ16, List AF17, Komrokji RS18, Padron E19, Sallman D20, Papaemmanuil E21, Campbell PJ22, Savona MR23, Seegmiller A24, Adès L25, Fenaux P26, Shih LY27, Bowen D28, Groves MJ29, Tauro S30, Fontenay M31, Kosmider O32, Bar-Natan M33, Steensma D34, Stone R35, Heuser M36, Thol F37, Cazzola M38, Malcovati L39, Karsan A40, Ganster C41, Hellström-Lindberg E42, Boultwood J43, Pellagatti A44, Santini V45, Quek L46, Vyas P47, Tüchler H48, Greenberg PL49, Bejar R50 |
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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 < 0.005), monosomal karyotype (p < 0.001), and high complexity, defined as more than 4 cytogenetic abnormalities (p < 0.001). Monosomal karyotype, high complexity, and TP53 mutation were individually associated with shorter overall survival, but monosomal status was not significant in a multivariable model. Multivariable survival modeling identified severe anemia (hemoglobin < 8.0 g/dL), NRAS mutation, SF3B1 mutation, TP53 mutation, elevated blast percentage (>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. |
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Publikations ID: 30635634 Quelle: öffnen |
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