NOTCH1在CLL患者中的突变情况及预后价值

Mutation and prognostic value of NOTCH1 gene in CLL patients

目的应用二代测序技术检测新疆地区慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)患者NOTCH1基因的突变情况,以及NOTCH1基因突变联合CLL-IPI预后评分系统对CLL患者的预后价值研究。方法收集初治CLL患者67例,进行NOTCH1基因突变检测,比较其在不同预后分组CLL患者中的突变情况,以及NOTCH1基因突变联合CLL-IPI对预后的影响。结果新疆地区初治CLL患者中NOTCH1基因突变率为20.9%,极高危组中患者的NOTCH1基因突变率为50%,高危组患者的NOTCH1基因突变率为22.7%,中危组患者的NOTCH1基因突变率为6.7%,低危组中没有患者发生NOTCH1基因突变。伴有NOTCH1基因突变患者的中位PFS(无进展生存期)时间较不伴有NOTCH1基因突变患者的中位PFS时间明显缩短,差异有统计学意义(P <0.05)。CLL-IPI分组中,高危组和极高危组中伴有NOTCH1基因突变患者的中位PFS时间明显短于不伴有NOTCH1基因突变的患者(P <0.05)。Cox多因素回归分析结果提示NOTCH1基因突变是影响CLL患者生存的独立预后因素(P <0.05)。结论 NOTCH1基因突变在CLL患者预示着预后不良,NOTCH1基因突变与CLL-IPI预后评分系统相结合更有利于精准判断CLL患者的预后。

Objective To detect the mutation of NOTCH1 gene in chronic lymphocytic leukemia(CLL)patients in Xinjiang through next-generation sequencing technology, and the prognostic value of NOTCH1 gene mutation combined with CLL-IPI prognostic scoring system for CLL patients were studied. Methods 67 newly diagnosed CLL patients were collected and mutation of NOTCH1 was detected.The mutations in different prognostic groups were compared, and the prognostic effect of NOTCH1 mutation combined with CLL-IPI were analyzed. Results The rate of NOTCH1 gene mutation in newly diagnosed CLL patients in Xinjiang was 20.9%. It was 50% in the extremely high-risk group and was 22.7% in the high-risk group, 6.7% in the medium-risk group, and no NOTCH1 gene mutation in the low-risk group. Compared with patients without NOTCH1 mutation, the median PFS of patients with NOTCH1 mutation was significantly shorter, and the difference was statistically significant(P < 0.05). In CLL-IPI groups, the median PFS of patients with NOTCH1 gene mutation in high-risk group and extremely high-risk group were significantly shorter than that of patients without NOTCH1 gene mutation(P < 0.05). Cox multivariate regression analysis indicated that NOTCH1 mutation was an independent prognostic factor affecting the survival of CLL patients(P < 0.05). Conclusion NOTCH1 gene mutation in CLL patients indicates poor prognosis, and the combination of NOTCH1 gene mutation and CLL-IPI prognostic scoring system is more conducive to accurately predict the prognosis of CLL patients.