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. 2022 Nov 25;6(12):e803.
doi: 10.1097/HS9.0000000000000803. eCollection 2022 Dec.

Distinct Immunogenetic Profiles of Chronic Lymphocytic Leukemia in Asia: A Taiwan Cooperative Oncology Group Registry Study

Chi-Yuan Yao  1   2   3 , Andreas Agathangelidis  4 , Shih-Sung Chuang  5 , Hsiao-Hui Tsou  6   7 , Wei-Lien Feng  8 , Ta-Chih Liu  9 , Tsai-Yun Chen  10 , Yuan-Bin Yu  11 , Su-Peng Yeh  12 , Ming Yao  1 , Chuan-Cheng Wang  13 , Johnson Lin  14 , Wen-Li Hwang  15 , Jyh-Pyng Gau  16 , Wen-Chien Chou  1   2 , Tsu-Yi Chao  17 , Liang-In Lin  18 , Hwei-Fang Tien  1 , Paolo Ghia  19 , Shang-Ju Wu  1   20
Affiliations

Distinct Immunogenetic Profiles of Chronic Lymphocytic Leukemia in Asia: A Taiwan Cooperative Oncology Group Registry Study

Chi-Yuan Yao et al. Hemasphere. .

Abstract

Asian patientswith chronic lymphocytic leukemia (CLL) exhibit immunoglobulin heavy variable (IGHV) gene repertoires that are distinct from those observed in Western populations, and a higher proportion of Asian CLL patients carry heavy loads of somatic hypermutations (SHM) within the B-cell receptor immunoglobulins (BcR IG). Due to the low regional incidence of CLL in Asia, only a limited number of studies had attempted to probe the phenomenon of BcR IG stereotypy in Asian populations. In this study, we analyzed the IGHV-IGHD-IGHJ gene rearrangements from a series of 255 CLL patients recruited in a nationwide, multicenter study in Taiwan. Our analysis revealed that the IGHV gene repertoire was characterized by evident biases, with IGHV3-7, IGHV4-34, and IGHV3-23 being the most frequent rearranged IGHV genes, and a higher proportion of cases carrying mutated IGHV. In terms of BcR stereotypy, the incidence of major subsets was less frequent in this cohort, with subsets #77 and #28A being the most common, while the incidence of minor subsets was approximately equivalent to that reported in the Western cohorts. With this study, we provide evidence that CLL in Asia is indeed associated with distinct immunogenetic characteristics regarding IGHV gene usage, SHM status, and BcR IG stereotypy.

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Figures

Figure 1.
Figure 1.
(A) Distribution of the IGHV gene usage in the TOCG cohort (N = 243). (B) Kaplan–Meier curves for overall survival (OS) of U-CLL versus M-CLL patients. CLL = chronic lymphocytic leukemia; IGHV = immunoglobulin heavy variable; M-CLL = mutated CLL; TCOG = Taiwan Cooperative Oncology Group; U-CLL = unmutated CLL.
Figure 2.
Figure 2.
Circos plot representation of the partnership of IGHV-IGHD-IGHJ gene recombinations in the TCOG cohort, displayed at the level of gene subgroups. The histograms below depict the percentage (y-axis) of the recombination partners for an individual IGHV or IGHD gene subgroup (color-coded, note the percentages of recombination partners for any given gene subgroup add up to 100%). IGHV = immunoglobulin heavy variable; TCOG = Taiwan Cooperative Oncology Group.
Figure 3.
Figure 3.
BcR IG stereotypy analysis in the TCOG cohort. (A) Distribution of VH CDR3 length in U-CLL vs M-CLL. (B) Stereotyped subsets were identified in around one-third of cases. (C) U-CLL had a higher proportion of stereotyped CLL cases, especially the major subsets. BcR IG = B-cell receptor immunoglobulins; CLL = chronic lymphocytic leukemia; IGHV = immunoglobulin heavy variable; M-CLL = mutated CLL; U-CLL = unmutated CLL.
Figure 4.
Figure 4.
The IGHV gene repertoire in stereotyped CLL cases vs the entire cohort. CLL = chronic lymphocytic leukemia; IGHV = immunoglobulin heavy variable.
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