Somatic Mutations Predict Poor Outcome in Patients With Myelodysplastic Syndrome After Hematopoietic Stem-Cell Transplantation
Somatic Mutations Predict Poor Outcome in Patients With Myelodysplastic Syndrome After Hematopoietic Stem-Cell Transplantation
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DOI：
10.1200/jco.2013.52.3381
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发表时间：
2014-09-01
影响因子：
45.3
通讯作者：
Ebert, Benjamin L.
中科院分区：
文献类型：
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作者：
Bejar, Rafael;Stevenson, Kristen E.;Ebert, Benjamin L.
目的骨髓增生异常综合征（MDS）中反复突变的基因是其致病的驱动因子，与临床表型和预后密切相关。这些类型的突变是否预测MDS患者异基因造血干细胞移植（HSCT）后的结果尚不清楚。Patients and MethodsWe used massive parallel sequencing to examinate tumor samples collected from 87 patients with MDS before HSCT for coding mutations in 40 recurrently mutated MDS genes.ResultsMutations were identified in 92% of patients，most frequently in the ASXL 1（29%），TP 53（21%）、DNMT 3A（18%）和RUNX 1（16%）基因。在单变量分析中，只有TP 53突变与较短的总体生存期（OS;风险比[HR]，3.74; P < .001）和无进展生存期（HR，3.97; P < .001）相关。在调整了与这些终点相关的临床变量后，TP 53基因突变（HR，2.30; P = .027），TET 2（HR，2.40; P = 0.033）和DNMT 3A（HR，2.08;在包括临床变量、复杂核型状态和候选基因的多变量分析中，TP 53（HR，4.22; P
PurposeRecurrently mutated genes in myelodysplastic syndrome (MDS) are pathogenic drivers and powerfully associated with clinical phenotype and prognosis. Whether these types of mutations predict outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with MDS is not known.Patients and MethodsWe used massively parallel sequencing to examine tumor samples collected from 87 patients with MDS before HSCT for coding mutations in 40 recurrently mutated MDS genes.ResultsMutations were identified in 92% of patients, most frequently in the ASXL1 (29%), TP53 (21%), DNMT3A (18%), and RUNX1 (16%) genes. In univariable analyses, only TP53 mutations were associated with shorter overall (OS; hazard ratio [HR], 3.74; P < .001) and progression-free survival (HR, 3.97; P < .001). After adjustment for clinical variables associated with these end points, mutations in TP53 (HR, 2.30; P = .027), TET2 (HR, 2.40; P = .033), and DNMT3A (HR, 2.08; P = .049) were associated with decreased OS. In multivariable analysis including clinical variables, complex karyotype status, and candidate genes, mutations in TP53 (HR, 4.22; P