Minimal residual disease detection and evolved IGH clones analysis in acute B lymphoblastic leukemia using IGH deep sequencing

Frontiers in Immunology

Wei Zhang¹  Xueyu Hong¹  Jinghua Wu¹  Xun Xu¹  Xiao Liu¹  Yuanping Du¹  Xuemei Li¹  Xiaojing Zeng¹  Changxi Wang¹  Jianhua Pan²  Shixi Liu³  Shan Jia³  Feiqiu Wen³  Xiuli Yuan³  Changgang Li³  Huirong Mai³  Xiaodong Wang³ 

[1] BGI-Shenzhen;KingMed Diagnostics;Shenzhen children’s hospital;

关键词: Clonal Evolution;    Minimal Residual Disease;    IGH;    High throughput sequencing (HTS);    acute B lymphoblast leukemia;   

DOI  :  10.3389/fimmu.2016.00403

来源: DOAJ

【 摘 要 】

Acute B lymphoblastic leukemia (B-ALL) is one of most common types of childhood cancer worldwide and chemotherapy is the main treatment approach. Despite good response rates to chemotherapy regiments, many patients eventually relapse and minimal residual disease (MRD) is the leading risk factor for relapse. The evolution of leukemic clones during disease development and treatment may have clinical significance. In this study, we performed immunoglobulin heavy chain (IGH) repertoire high throughput sequencing (HTS) on the diagnostic and post-treatment samples of 51 pediatric B-ALL patients. We identified leukemic IGH clones in 92.2% of the diagnostic samples and nearly half of the patients were polyclonal. About 1/3 of the leukemic clones have correct open reading frame (ORF) in the complementarity determining region 3 (CDR3) of IGH, which demonstrates that the leukemic B cells were in the early developmental stage. We also demonstrated the higher sensitivity of HTS in MRD detection and investigated the clinical value of using peripheral blood in MRD detection and monitoring the clonal IGH evolution. In addition, we found leukemic clones were extensively undergoing continuous clonal IGH evolution by variable gene replacement. Dynamic frequency change and newly emerged evolved IGH clones were identified upon the pressure of chemotherapy. In summary, we confirmed the high sensitivity and universal applicability of HTS in MRD detection. We also reported the ubiquitous evolved IGH clones in B-ALL samples and their response to chemotherapy during treatment.

【 授权许可】

Unknown