Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia
Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia
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DOI：
10.3324/haematol.2008.005272
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发表时间：
2009-10-01
期刊：
影响因子：
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通讯作者：
Hofmann, Wolf-Karsten
中科院分区：
文献类型：
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作者：
Baldus, Claudia D.;Thibaut, Julia;Hofmann, Wolf-Karsten
NOTCH1突变与儿童急性T淋巴细胞白血病的良好预后相关，然而，关于NOTCH1突变对成人T淋巴细胞白血病预后意义的研究结果仍然存在争议。设计与方法在大量成人T淋巴细胞白血病患者(n=126)中，我们调查了NOTCH1通路突变，特别是NOTCH1和FBXW7基因突变对预后的影响。结果NOTCH1和FBXW7基因分别有57%和12%发生突变。携带NOTCH1和/或FBXW7(NOTCH1-FBXW7)突变的患者的特征与野生型相似，NOTCH1-FBXW7突变患者在总体队列中更多地表现为胸腺免疫表型(p=0.001)；在完全缓解或无事件生存率方面，NOTCH1-FBXW7突变患者与野生型NOTCH1-FBXW7患者之间没有显著差异(p=0.39)。但在低风险ERG/BAALC表达状态的一小部分患者中，NOTCH1-FBXW7突变对预后有有利影响的趋势。我们的发现进一步证实了NOTCH1突变在成人T淋巴细胞白血病中的高频率
BackgroundNOTCH1 mutations have been associated with a favorable outcome in pediatric acute T-lymphoblastic leukemia However, the results of studies on the prognostic significance of NOTCH1 mutations in adult T-lymphoblastic leukemia remain controversial.Design and MethodsHere we have investigated the prognostic impact of mutations in the NOTCH1 pathway, in particular, the NOTCH1 and FBXW7 genes, in a large cohort of adult patients with T-lymphoblastic leukemia (n=126). We determined the occurrence Of Mutations In NOTCH1 and FBXW7 by DNA amplification and direct sequencing of polymerase chain reaction productsResultsMutations were identified in 57% and 12% of the NOTCH1 and FBXW7 genes, respectively. The characteristics of patients carrying NOTCH1 and/or FBXW7 (NOTCH1-FBXW7) mutations were similar to those with wild-type genes Patients with NOTCH1-FBXW7 mutations more often showed a thymic immunophenotype (p=0.001) In the over-all cohort; no significant differences were seen in the complete remission or event-free survival rates between patients with mutated or wild-type NOTCH1-FBXW7 (p=0.39)ConclusionsNOTCH1 and FBXW7 mutations were not predictive of outcome in the overall cohort of adult patients with T-lymphoblastic leukemia. but there was a trend towards a favorable prognostic impact of NOTCH1-FBXW7 mutations in the small subgroup of patients with low-risk ERG/BAALC expression status. Our findings further confirm the high frequency of NOTCH1 mutations in adult T-lymphoblastic leukemia