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

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.

The mystery of chronic lymphocytic leukemia (CLL): Why is it absent in Asians and what does this tell us about etiology, pathogenesis and biology?

“…These distributions have changed slightly in an unpublished final analysis but P-values remain mostly unchanged (personal communication). A significantly higher frequency of subset-8 was also seen in Chinese (10% vs. 1%; P b 0.01) [38].…”

“…D3-03 was significantly under-represented whereas DH6, D6-13 and D3-10 were significantly over-represented in Chinese with CLL. Chinese with CLL also had significantly less stereotyped receptors (14% vs. 31%; P = 0.0001) [38]. These distributions have changed slightly in an unpublished final analysis but P-values remain mostly unchanged (personal communication).…”

“…Chinese and Japanese with CLL initially seemed to have a higher proportion of cases with mutated IGHV probably exceeding 70-90% [17,37]. However, as sample size has increased the proportion of Chinese with mutated IGHV decreased to about 60% typical of persons of predominately European descent with CLL [38].…”

“…In Asians and persons of predominately European descent with CLL IGHV 4-34, IGHV 3-07, IGHV 3-23 and IGHV 3-30 are commonly rearranged [14,17,36,37,40,41,45]. Recently, a direct comparison reported that V1-69 and V1-02 were under-represented in Chinese with CLL whereas V4-59, V3-07 and V4-39 were over-represented compared with Italians with CLL [38].…”

Effect of IGHV Gene Mutation Status and BCR Structure Stereotypy on Effectiveness of BR Regimen in First-Line Therapy of Chronic Lymphocytic Leukemia

“…Как и в других европейских работах [19], среди раз-личных вариантов стереотипности в исследованной российской выборке преобладали стереотипные группы № 2 (n = 11) и 1 (n = 5). Относительно часто встречались варианты, принадлежащие к стерео-типным группам № 7 (n = 5) и 8 (n = 4).…”