Mounting evidence indicates that immunoglobulin variable heavy-chain (IGHV) repertoire and mutational status in chronic lymphocytic leukemia (CLL) patients are prognostically relevant. However, rare data is available in Chinese CLL population. Our group investigated 270 Chinese CLL patients for their IGHV sequences and discovered significant differences between Chinese and European CLL patients. First of all, 169 (62.6%) patients in our group got mutated IGHV and 101 (37.4%) were unmutated, rendering a considerable higher percentage of mutated subgroup compared with European patients (55%) (Figure 1). While IGVH3 is still the most frequently used IGVH gene in Chinese CLL patients (135/270, 50%), discrepancy occurs in the usage of IGVH1 gene, which only presents in 13.7% (37/274) patients in our cohort whereas 23.79% for European (Figure 2). Regarding IGHV subgroups, IGHV3-23 and IGHV4-34 are more often used in Chinese CLL patients (10.7% and 10.4%, respectively). Remarkably, IGHV1-69, the most prevalent IGHV subgroup in European CLL patients (12.81%), only accounts for 5.2% (14/270) Chinese cases.
Figure 1
Figure 1. Higher percentage of mutated IGHV in Chinese CLL patients
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Higher percentage of mutated IGHV in Chinese CLL patients

Figure 1
Figure 1. Higher percentage of mutated IGHV in Chinese CLL patients
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Higher percentage of mutated IGHV in Chinese CLL patients

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Figure 2
Figure 2. Different IGHV gene usage between Chinese and European CLL patients, with IGVH1 gene accounts for 23.79% of European CLL patients and for only 13.70% of Chinese CLL patients.
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Different IGHV gene usage between Chinese and European CLL patients, with IGVH1 gene accounts for 23.79% of European CLL patients and for only 13.70% of Chinese CLL patients.

Figure 2
Figure 2. Different IGHV gene usage between Chinese and European CLL patients, with IGVH1 gene accounts for 23.79% of European CLL patients and for only 13.70% of Chinese CLL patients.
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Different IGHV gene usage between Chinese and European CLL patients, with IGVH1 gene accounts for 23.79% of European CLL patients and for only 13.70% of Chinese CLL patients.

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Figure 3
Figure 3. IGVH1-69 is the most prevalent IGHV gene among European CLL patients(12.81%), however, only 5.20% Chinese CLL patients use VH1-69. IGVH4-39 and IGVH4-59 are more often used in Chinese CLL patients (7.80% vs 3.73% and 5.60% vs 2.75%, respectively).
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IGVH1-69 is the most prevalent IGHV gene among European CLL patients(12.81%), however, only 5.20% Chinese CLL patients use VH1-69. IGVH4-39 and IGVH4-59 are more often used in Chinese CLL patients (7.80% vs 3.73% and 5.60% vs 2.75%, respectively).

Figure 3
Figure 3. IGVH1-69 is the most prevalent IGHV gene among European CLL patients(12.81%), however, only 5.20% Chinese CLL patients use VH1-69. IGVH4-39 and IGVH4-59 are more often used in Chinese CLL patients (7.80% vs 3.73% and 5.60% vs 2.75%, respectively).
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IGVH1-69 is the most prevalent IGHV gene among European CLL patients(12.81%), however, only 5.20% Chinese CLL patients use VH1-69. IGVH4-39 and IGVH4-59 are more often used in Chinese CLL patients (7.80% vs 3.73% and 5.60% vs 2.75%, respectively).

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We further studied the distribution of stereotyped BCR in our cohort. Thirty-eight patients (14.07%) with stereotyped BCR that belonged to 21 subsets were identified, with 1 to 7 sequences contained each. Among them, subset 1 and subset 8 are the most common types with 6 and 7 cases respectively. Three new subsets were discovered (Table 1). Notably, only 1 case belonged to subset 2, the subset with largest group size in western world. Hence, we conclude that Chinese CLL patients show unique IGHV repertoire features compared to patients from western countries. While the mechanism within remains unknown, the discrepancy might due to antigenic difference in geographically remote areas.

Table 1

Three new subsets of BCR stereotypy in Chinese CLL patients

NO.IGHVIGHDIGHJM/UMIdentityHCDR3 AA sequenceLength
Novel 1 NJ-15 IGHV4-59*08 3-22*01 6*03 UM 100,00% ARGNYYDSSGYYYVGYYYYYMDV 23 
 NJ-31 IGHV4-59*01 3-22*01 6*03 UM 99,65% ARGDYYDSSGYYYVGYYYYYMDV 23 
Novel 2 NJ-186 IGHV3-23*01 3-22*01 4*02 M 96.60% AKGYRDNYDGDQSSVFDS 18 
 NJ-23 IGHV3-23*01 2-21*01 4*02 M 96,53% AKGYRDNYDGDQSSVFDS 18 
Novel 3 NJ-36 IGHV4-34*01 6-6*01 5*02 M 93,33% AKLMAGRPNWFDP 13 
 NJ-123 IGHV4-34*01 6-6*01 5*02 M 91,67% AKLMAGRPNWFDP 13 
NO.IGHVIGHDIGHJM/UMIdentityHCDR3 AA sequenceLength
Novel 1 NJ-15 IGHV4-59*08 3-22*01 6*03 UM 100,00% ARGNYYDSSGYYYVGYYYYYMDV 23 
 NJ-31 IGHV4-59*01 3-22*01 6*03 UM 99,65% ARGDYYDSSGYYYVGYYYYYMDV 23 
Novel 2 NJ-186 IGHV3-23*01 3-22*01 4*02 M 96.60% AKGYRDNYDGDQSSVFDS 18 
 NJ-23 IGHV3-23*01 2-21*01 4*02 M 96,53% AKGYRDNYDGDQSSVFDS 18 
Novel 3 NJ-36 IGHV4-34*01 6-6*01 5*02 M 93,33% AKLMAGRPNWFDP 13 
 NJ-123 IGHV4-34*01 6-6*01 5*02 M 91,67% AKLMAGRPNWFDP 13 
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Disclosures:

No relevant conflicts of interest to declare.

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