期刊
LEUKEMIA
卷 33, 期 7, 页码 1747-1758出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41375-018-0351-2
关键词
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资金
- MDS Foundation
- Celgene
- MRC Disease Team Awards [G1000729/94931, MR/L008963/1]
- MRC Molecular Haematology Unit
- Oxford Partnership Comprehensive Biomedical Research Centre (NIHR BRC Funding scheme) [oxfbrc-2012-1]
- MRC Clinician Scientist Fellowship
- Bloodwise (UK)
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [20125]
- DFG [HE 5240/6-1]
- [K08 DK091360]
- MRC [G1000729, MR/L008963/1, MR/R007608/1, MC_UU_00016/11, MC_UU_12009/11, MC_U137961146] Funding Source: UKRI
- National Institutes of Health Research (NIHR) [oxfbrc-2012-1] Funding Source: National Institutes of Health Research (NIHR)
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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