【摘要】 目的：探讨携带exportin 1(XPO1)基因突变的慢性淋巴细胞白血病（chronic lymphocytic leukemia,CLL）患者的临床特征，为临床诊治提供线索。方法：回顾性分析2006年11月—2022年3月就诊于南京医科大学第一附属医院血液科、且检测出XPO1基因突变的CLL患者临床资料，比较初诊未治（treatment native,TN）和复发/难治（relapsed/refractory,R/R）XPO1突变患者的临床数据、治疗反应及生存结局。结果：在543例CLL患者中，15例（2.8%）患者XPO1基因突变检测阳性，TN组（368例）、R/R组（175例）中患者的突变率分别为9例（2.4%）及6例（3.4%），存在热点突变（E571K）。患者疾病分期多为RaiⅢ/Ⅳ期，Binet B/C组，且免疫球蛋白重链可变区基因（immunoglobulin heavy-chain variable region,IGHV）无突变。XPO1基因突变与NOTCH1、SF3B1、KMT2D、TP53等基因可同时出现，且与疾病状态无关，而TP53与XPO1基因突变同时发生多见于R/R组（TN:11.1%;R/R:50.0%）。XPO1突变患者的中位至首次治疗时间（time to first treatment,TTFT）为1.8个月，中位无进展生存期（progression-free survival,PFS）为19.8个月，中位总生存时间（overall survival,OS）为40.0个月；XPO1无突变组患者TTFT为8.1个月，PFS为32.5个月，OS为49.8个月。结论：XPO1突变在CLL中为低频突变且常伴随其他基因突变同时发生。R/R患者携带XPO1突变多于TN患者，且肿瘤负荷更高。XPO1突变组患者的TTFT、PFS较XPO1无突变组患者趋向于更短。更多还原

【Abstract】 Objective:To investigate the clinical characteristics of patients with chronic lymphocytic leukemia(CLL)carrying exportin 1(XPO1)mutations,providing clues for clinical diagnosis and treatment. Methods:The clinical data of CLL patients with XPO1 mutations detected in the Department of Hematology of the First Affiliated Hospital of Nanjing Medical University from November 2006 and March 2022 were retrospectively analyzed. The clinical data,treatment responses,and survival outcomes of the treatment native(TN)and relapsed/refractory(R/R)patients with XPO1 mutation were compared. Results:Among 543 CLL patients,15 patients(2.8%)tested positive with XPO1 mutations. The mutation rates in the TN group(368 cases)and R/R group(175 cases)were 2.4%(9 cases)and 3.4%(6 cases),respectively,with a hotspot mutation(E571K)identified. Most of the patients were in Rai Ⅲ/Ⅳ stage and Binet B/C group,and had no mutations in the immunoglobulin heavy-chain variable region(IGHV). XPO1 gene mutation co-occurred with NOTCH1,SF3B1,KMT2D,TP53,and other gene mutations,with TP53 and XPO1 mutations more common in the R/R group(TN:11.1%;R/R:50%). The median time to first treatment(TTFT)for patients with XPO1 mutations was 1.8 months,the median progression-free survival(PFS)was 19.8 months,and the median overall survival(OS)was 40.0 months. In the XPO1 nonmutated patients,TTFT was 8.1 months,PFS was 32.5 months,and OS was 49.8 months. Conclusion:XPO1 mutations in CLL are lowfrequency mutations often occurring simultaneously with other gene mutations. R/R patients are more likely to carry XPO1 mutations than TN patients,with a higher tumor burden. XPO1 mutated patients tend to have shorter TTFT and PFS,compared with those without XPO1 mutations.更多还原