Notch-1 mutations are secondary events in some patients with T-Cell acute lymphoblastic leukemia
Notch-1 mutations are secondary events in some patients with T-Cell acute lymphoblastic leukemia
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DOI：
10.1158/1078-0432.ccr-07-1474
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发表时间：
2007-12-01
影响因子：
11.5
通讯作者：
Linchl, David C.
中科院分区：
文献类型：
--
作者：
Mansour, Marc R.;Duke, Veronique;Linchl, David C.
目的：Notch-1 激活突变在 T 细胞急性淋巴细胞白血病 (T-ALL) 中很常见，> 50% 的患者发生这种情况。在 T-ALL 小鼠模型中，Notch-1 激活既可以直接引发白血病，又可以继发性地协同其他原发事件。 Notch-1 突变的获得是人类 T-ALL 发病机制中的早期起始事件还是继发事件尚不清楚。实验设计：我们使用变性高效液相色谱、测序和片段分析来分析 62 名就诊患者以及 16 例匹配的就诊复发样本中的 Notch-1 突变状态和突变水平。结果：我们在 47 名患者 (76%) 中检测到了 Notch-1 突变。其中七个是低水平突变（量化为
Purpose: Activating Notch-1 mutations are frequent in T-cell acute lymphoblastic leukemia (T-ALL), occurring in > 50% of patients. In murine models of T-ALL, Notch-1 activation can both directly initiate leukemia and cooperate secondarily to other primary events. Whether acquisition of Notch-1 mutations is an early initiating event or a secondary event in the pathogenesis of human T-ALL is unclear.Experimental Design: We used denaturing high-performance liquid chromatography, sequencing, and fragment analysis to analyze Notch-1 mutational status and mutant level in 62 patients at presentation as well as 16 matched presentation-relapse samples.Results: We detected Notch-1 mutations in 47 patients (76%). Seven of these were low-level mutations (quantified at