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Landscape of immunoglobulin heavy chain gene repertoire and its clinical relevance to LPL/WM

Lymphoplasmacytic lymphoma/Waldenstro?m macroglobulinemia (LPL/WM) is a heterogeneous disease in which the role of immunoglobulin heavy chain genes (IGH) remains unknown. To determine the clinical relevance of the IGH repertoire in LPL/WM patients, we performed immunoglobulin gene rearrangement and...

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Bibliographic Details
Published in:Blood advances 2022-07, Vol.6 (13), p.4049-4059
Main Authors: Wang, Jun, Yan, Yuting, Xiong, Wenjie, Song, Ge, Wang, Yi, Zhao, Jiawei, Jia, Yujiao, Li, Chengwen, Yu, Zhen, Yu, Ying, Chen, Jiawen, Jiao, Yang, Wang, Tingyu, Lyu, Rui, Li, Qinghua, Ma, Yueshen, Liu, Wei, Zou, Dehui, An, Gang, Sun, Qi, Wang, Huijun, Xiao, Zhijian, Wang, Jianxiang, Qiu, Lugui, Yi, Shuhua
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Language:English
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Summary:Lymphoplasmacytic lymphoma/Waldenstro?m macroglobulinemia (LPL/WM) is a heterogeneous disease in which the role of immunoglobulin heavy chain genes (IGH) remains unknown. To determine the clinical relevance of the IGH repertoire in LPL/WM patients, we performed immunoglobulin gene rearrangement and complementarity determining region 3 (CDR3) analysis. The IGH variable gene repertoire was remarkably biased in LPL/WM. IGHV3-23, IGHV4-34, IGHV3-30, IGHV3-7, and IGHV3-74 accounted for half of the cohorts’ repertoire. Most cases (97.1%) were found to carry mutated IGHV genes, based on a 98% IGHV germline homology cutoff. IGHV3-30 was associated with long heavy chain CDR3, indicating there was specific antigen selection in LPL/WM. Patients with IGHV3-7 were significantly more likely to harbor the 6q deletion (P
ISSN:2473-9529
2473-9537
DOI:10.1182/bloodadvances.2022007279