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. 2019 Oct;187(1):82-92.
doi: 10.1111/bjh.16051. Epub 2019 Jun 23.

Distinct immunoglobulin heavy chain variable region gene repertoire and lower frequency of del(11q) in Taiwanese patients with chronic lymphocytic leukaemia

Ying-Jung Huang  1 , Ming-Chung Kuo  1   2 , Hung Chang  1   2 , Po-Nan Wang  1 , Jin-Hou Wu  1 , Yen-Min Huang  3 , Ming-Chun Ma  4 , Tzung-Chih Tang  1 , Ching-Yuan Kuo  4 , Lee-Yung Shih  1   2
Affiliations

Distinct immunoglobulin heavy chain variable region gene repertoire and lower frequency of del(11q) in Taiwanese patients with chronic lymphocytic leukaemia

Ying-Jung Huang et al. Br J Haematol. 2019 Oct.

Abstract

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in Western countries but very rare in Asia. Peripheral blood or bone marrow mononuclear cells obtained at initial diagnosis from 194 patients with CLL were analysed to determine the ethnic difference in genetic abnormalities. Mutated IGHV was detected in 71·2% of Taiwanese CLL and IGHV3-23 was the most frequently used gene. Stereotyped BCR was present in 18·3% with subset 8 being the most frequent. All cases with subset 8 belonged to IGHV 4-39 and were exclusively associated with un-mutated IGHV and poor outcome. Mutation frequencies of SF3B1 (9·7%), NOTCH1 (8·6%), BIRC3 (1·1%), ATM (16·9%) or TP53 (8·1%), and frequencies of cytogenetic abnormalities including trisomy 12 (18·6%), del(17p) (10·4%), del(13q) (43·7%) and IGH translocation (10·1%) were comparable to those reported from Western countries, except del(11q) (6·9%) which was lower in our patients. Patients with un-mutated IGHV, subset 8, disrupted TP53, trisomy 12, and SF3B1 mutations had a worse outcome compared to patients without these mutations. In conclusion, IGHV3-23 usage, stereotyped subset 8 and lower frequency of del(11q) show an ethnicity-dependent association in Taiwanese CLL patients.

Keywords: ATM; IGHV; TP53; BCR stereotype; chronic lymphocytic leukaemia.

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Conflict of interest statement

The authors have no conflict interest.

Figures

Figure 1
Figure 1
(A) Distribution of IGHV usage in 191 chronic lymphocytic leukaemia patients; (B) Number of mutated IGHV in the most frequent subtypes.
Figure 2
Figure 2
Correlation among the genetic lesions in 194 patients with chronic lymphocytic leukaemia. Areas not examined are indicated in grey. BCR, B‐cell receptor.
Figure 3
Figure 3
Kaplan–Meier estimates of (A) treatment‐free survival and (B) overall survival according to TP53 disruption and IGHV mutational status in Taiwanese chronic lymphocytic leukaemia patients.
See this image and copyright information in PMC

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