Charité, University Hospital Berlin, Campus Benjamin Franklin, Department of Hematology and Oncology, Hindenburgdamm 30 12203 Berlin, Germany.
Haematologica. 2009 Oct;94(10):1383-90. doi: 10.3324/haematol.2008.005272.
NOTCH1 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.
Here 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 products.
Mutations 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 overall 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).
NOTCH1 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.
NOTCH1 突变与儿科急性 T 淋巴细胞白血病的良好预后相关。然而，NOTCH1 突变在成人 T 淋巴细胞白血病中的预后意义的研究结果仍存在争议。
在此，我们研究了 NOTCH1 通路突变，特别是 NOTCH1 和 FBXW7 基因，在一个大型成人 T 淋巴细胞白血病患者队列（n=126）中的预后影响。我们通过 DNA 扩增和聚合酶链反应产物的直接测序来确定 NOTCH1 和 FBXW7 中的突变发生情况。
分别在 57%和 12%的 NOTCH1 和 FBXW7 基因中鉴定出突变。携带 NOTCH1 和/或 FBXW7（NOTCH1-FBXW7）突变的患者的特征与具有野生型基因的患者相似。具有 NOTCH1-FBXW7 突变的患者更常表现为胸腺免疫表型（p=0.001）。在整个队列中，突变型和野生型 NOTCH1-FBXW7 患者的完全缓解率或无事件生存率之间没有显著差异（p=0.39）。
在总体成人 T 淋巴细胞白血病患者队列中，NOTCH1 和 FBXW7 突变不能预测预后，但在 ERG/BAALC 表达状态低危的小亚组患者中，NOTCH1-FBXW7 突变具有良好的预后影响趋势。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。
