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

Jun WangYuting YanWenjie XiongGe SongYi WangJiawei ZhaoYujiao JiaChengwen LiZhen YuYing YuJiawen ChenYang JiaoTingyu WangRui LvQinghua LiYueshen MaWei LiuDehui ZouGang AnQi SunHuijun WangZhijian XiaoJian-Xiang WangLugui QiuShuhua Yi
Published in: Blood advances (2022)
Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) is a heterogeneous disease in which the role of immunoglobulin heavy-chain genes (IGHs) remains unknown. To determine the clinical relevance of the IGH repertoire in patients with LPL/WM, we performed immunoglobulin gene rearrangement and complementarity determining region 3 (CDR3) analysis. The IGH variable gene (IGHV) repertoire was remarkably biased in LPL/WM. IGHV3-23, IGHV4-34, IGHV3-30, IGHV3-7, and IGHV3-74 accounted for one-half of the cohort's 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 < .001) and an abnormal karyotype (P = .004). The IGHV hypermutation rate in patients with the MYD88 L265P mutation was significantly higher than that of wild-type patients (P = .050). IGHV3-23 and IGHV3-74 segments were more frequently detected in patients with MYD88-mutated LPL/WM (P = .050), whereas IGHV3-7 presented more frequently in MYD88 wild-type patients (P = .042). Patients with IGHV4, especially IGHV4-34, had higher levels of lactate dehydrogenase, and IGHV4 was a predictive marker of shorter progression-free survival. These results showed for the first time that the IGHV repertoire has clinical relevance in LPL/WM.
Keyphrases
  • wild type
  • end stage renal disease
  • ejection fraction
  • chronic kidney disease
  • gene expression
  • newly diagnosed
  • oxidative stress
  • inflammatory response
  • peritoneal dialysis
  • genome wide identification
  • single cell