Immunoglobulin gene rearrangements in Chinese and Italian patients with chronic lymphocytic leukemia.

M Marinelli ,Wei Xu,Irene Della Starza,Anna Guarini,Luciana Cafforio,Lugui Qiu,Zhen Yu,Ilaria Del Giudice,Eric Tse,Robin Foà,Wenjuan Yang,Paola Mariglia,Silvia Bonina,Yi Xia,Caterina Ilari,Alfonso Piciocchi,Jianyong Li,Sara Raponi,Tk Chan ,Yok Lam Kwong

doi:10.18632/oncotarget.7819

Abstract

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.

Highlights

Chronic lymphocytic leukemia (CLL) is characterized by a variable clinical course, driven by the immunogenetic and molecular heterogeneity of the disease [1,2,3,4,5].The heterogeneity of CLL is reflected by the different incidence in populations with diverse ethnic and geographic distribution
The IGHVDJ subgroup and gene usage were for the most part comparable to those reported in previous studies [28,29,30,31], showing no relevant differences in the frequency of the most representative genes
When we examined the IGHV genes, the most frequently encountered were IGHV1-69 (110; 13.9%), IGHV4-34 (77; 9.7%), IGHV3-23 (51; 6.4%), IGHV3-30 (46; 5.8%), IGHV1-2 (44; 5.6%), IGHV3-7 (42; 5.3%), IGHV3-11 (31; 3.9%), IGHV3-21 (30; 3.8%), IGHV348 (28; 3.5%), IGHV4-39 (27; 3.4%), IGHV3-33 (27; 3.4%); collectively, these genes accounted for 65% of the cases, in line with the reported features of Caucasian CLL (Supplementary Table S1B)

Summary

Introduction

Chronic lymphocytic leukemia (CLL) is characterized by a variable clinical course, driven by the immunogenetic and molecular heterogeneity of the disease [1,2,3,4,5].The heterogeneity of CLL is reflected by the different incidence in populations with diverse ethnic and geographic distribution. Chronic lymphocytic leukemia (CLL) is characterized by a variable clinical course, driven by the immunogenetic and molecular heterogeneity of the disease [1,2,3,4,5]. The age-adjusted incidence rate (AAIR) is about 4.4 new cases x 100.000 individuals/year in the US (2007-2011) [8]. The AAIR in Asians is about 10 times lower, with 0.2-0.3 new cases x 100.000 individuals/year [8, 9]. The reasons for this epidemiologic heterogeneity remain to be defined. The genetic background is important in determining the risk of the disease, beyond potential environmental factors

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