Marinelli Marilisa, Ilari Caterina, Xia Yi, Del Giudice Ilaria, Cafforio Luciana, Della Starza Irene, Raponi Sara, Mariglia Paola, Bonina Silvia, Yu Zhen, Yang Wenjuan, Qiu Lugui, Chan Thomas, Piciocchi Alfonso, Kwong Yok-Lam, Tse Eric, Li Jianyong, Guarini Anna, Xu Wei, Foà Robin
Department of Cellular Biotechnologies and Hematology, "Sapienza" University, Rome, Italy.
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
Oncotarget. 2016 Apr 12;7(15):20520-31. doi: 10.18632/oncotarget.7819.
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western world, whereas in Asia the incidence is about 10 times lower. The basis for this ethnic and geographic variation is currently unknown. The aim of this study was to characterize IGHVDJ rearrangements and stereotype of the HCDR3 region in a series of 623 Chinese CLL, in order to identify possible differences in immunoglobulin gene usage and their potential pathogenetic implications. Chinese CLL were compared to 789 Italian CLL. Chinese patients showed a higher proportion of mutated IGHV and a more frequent usage of IGHV3-7, IGHV3-74, IGHV4-39 and IGHV4-59 genes. A significantly lower usage of IGHV1-69 and IGHV1-2 was documented, with comparable IGHV3-21 frequency (3% Chinese vs 3.8% Italian CLL). The proportion of known stereotyped receptors was significantly lower in Chinese (19.7%) than in Italian CLL (25.8%), despite a significantly higher frequency of subset #8 (p= 0.0001). Moreover, new paired clusters were identified among Chinese cases. Overall, these data support a potential different antigenic exposure between Eastern and Western CLL.
慢性淋巴细胞白血病(CLL)是西方世界最常见的白血病类型,而在亚洲其发病率约低10倍。目前尚不清楚这种种族和地理差异的基础。本研究的目的是对623例中国CLL患者的IGHVDJ重排和HCDR3区域的模式进行特征分析,以确定免疫球蛋白基因使用方面可能存在的差异及其潜在的致病意义。将中国CLL患者与789例意大利CLL患者进行比较。中国患者显示出IGHV突变比例更高,且IGHV3-7、IGHV3-74、IGHV4-39和IGHV4-59基因的使用频率更高。记录到IGHV1-69和IGHV1-2的使用频率显著更低,IGHV3-21频率相当(中国CLL患者为3%,意大利CLL患者为3.8%)。尽管亚群#8的频率显著更高(p = 0.0001),但中国CLL患者中已知模式化受体的比例(19.7%)显著低于意大利CLL患者(25.8%)。此外,在中国病例中发现了新的配对簇。总体而言,这些数据支持东西方CLL患者可能存在不同的抗原暴露。