| Autor: |
Sallman, D A, Komrokji, R, Vaupel, C, Cluzeau, T, Geyer, S M, McGraw, K L, Al Ali, N H, Lancet, J, McGinniss, M J, Nahas, S, Smith, A E, Kulasekararaj, A, Mufti, G, List, A, Hall, J, Padron, E |
| Zdroj: |
Leukemia; March 2016, Vol. 30 Issue: 3 p666-673, 8p |
| Abstrakt: |
Although next-generation sequencing has allowed for the detection of somatic mutations in myelodysplastic syndromes (MDS), the clinical relevance of variant allele frequency (VAF) for the majority of mutations is unknown. We profiled TP53and 20 additional genes in our training set of 219 patients with MDS or secondary acute myeloid leukemia with findings confirmed in a validation cohort. When parsed by VAF, TP53VAF predicted for complex cytogenetics in both the training (P=0.001) and validation set (P<0.0001). MDS patients with a TP53VAF > 40% had a median overall survival (OS) of 124 days versus an OS that was not reached in patients with VAF <20% (hazard ratio (HR), 3.52; P=0.01) with validation in an independent cohort (HR, 4.94, P=0.01). TP53VAF further stratified distinct prognostic groups independent of clinical prognostic scoring systems (P=0.0005). In multivariate analysis, only a TP53VAF >40% was an independent covariate (HR, 1.61; P<0.0001). In addition, SRSF2VAF predicted for monocytosis (P=0.003), RUNX1VAF with thrombocytopenia (P=0.01) and SF3B1with ringed sideroblasts (P=0.001). Together, our study indicates that VAF should be incorporated in patient management and risk stratification in MDS. |
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