Institute of Hematology, Medical College, Jinan University, Guangzhou 510632, People's Republic of China.
Cancer Cell Int. 2012 Apr 5;12:13. doi: 10.1186/1475-2867-12-13.
The Notch signaling pathway is crucial in T-cell development, Notch1 mutations are frequently present in T-cell acute lymphoblastic leukemia (T-ALL). To investigate the feature of Notch1 mutation and its corresponding expression level in Chinese patients with T-ALL, detection of mutation and the expression level of Notch1 gene was preformed using RT-PCR, sequencing and real-time PCR respectively.
Two Notch1 point mutations (V1578E and L1593P) located on HD-N domain were identified in three cases out of 13 T-ALL patients. The mutation on 4733 position (V1578E) found in two cases was a novel mutation. The overexpression of Notch1 was detected in all samples with T-ALL, moreover, significantly higher expression of Notch1 was detected in the T-ALL with Notch1 mutation group compared with T-ALL with WT Notch1 group (p = 0.0192).
Higher expression of Notch1 was associated with Notch1 mutation, more novel mutation of this gene might be identified in different populations and its contribution to the molecular pathogenesis of T-ALL is needed further research.
Notch 信号通路在 T 细胞发育中至关重要，Notch1 突变在 T 细胞急性淋巴细胞白血病（T-ALL）中经常存在。为了研究 Notch1 突变及其在中国 T-ALL 患者中的相应表达水平的特征，我们分别使用 RT-PCR、测序和实时 PCR 检测了突变和 Notch1 基因的表达水平。
在 13 例 T-ALL 患者中，有 3 例发现了位于 HD-N 结构域的两个 Notch1 点突变（V1578E 和 L1593P）。在两个病例中发现的 4733 位（V1578E）突变是一种新的突变。所有 T-ALL 样本均检测到 Notch1 的过表达，并且 Notch1 突变组的 Notch1 表达显著高于 WT Notch1 组（p = 0.0192）。
Notch1 的高表达与 Notch1 突变相关，在不同人群中可能会发现更多 Notch1 基因的新突变，其对 T-ALL 分子发病机制的贡献需要进一步研究。
