title: Minimal Residual Disease Detection and EvolvedIGHClones Analysis in Acute B Lymphoblastic Leukemia UsingIGHDeep Sequencing.
abstract: Acute B lymphoblastic leukemia (B-ALL) is one of the 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 leukemicIGHclones in 92.2% of the diagnostic samples and nearly half of the patients were polyclonal. About one-third of the leukemic clones have correct open reading frame in the complementarity determining region 3 (CDR3) ofIGH, 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 clonalIGHevolution. In addition, we found leukemic clones were extensively undergoing continuous clonalIGHevolution by variable gene replacement. Dynamic frequency change and newly emerged evolvedIGHclones 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 evolvedIGHclones in B-ALL samples and their response to chemotherapy during treatment.
authors.affiliation: BGI-Shenzhen, Shenzhen, China; China National Genebank-Shenzhen, BGI-Shenzhen, Shenzhen, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Wu
authors.affiliation: Hematology and Oncology Department, Shenzhen Children's Hospital , Shenzhen , China.
authors.forename: Shan
authors.initials: S
authors.lastname: Jia
authors.affiliation: BGI-Shenzhen, Shenzhen, China; China National Genebank-Shenzhen, BGI-Shenzhen, Shenzhen, China.
authors.forename: Changxi
authors.initials: C
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen, China; China National Genebank-Shenzhen, BGI-Shenzhen, Shenzhen, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Hematology and Oncology Department, Shenzhen Children's Hospital , Shenzhen , China.
authors.forename: Sixi
authors.initials: S
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Shenzhen, China; China National Genebank-Shenzhen, BGI-Shenzhen, Shenzhen, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Hematology and Oncology Department, Shenzhen Children's Hospital , Shenzhen , China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Mai
authors.affiliation: Hematology and Oncology Department, Shenzhen Children's Hospital , Shenzhen , China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Yuan
authors.affiliation: BGI-Shenzhen, Shenzhen, China; China National Genebank-Shenzhen, BGI-Shenzhen, Shenzhen, China.
authors.forename: Yuanping
authors.initials: Y
authors.lastname: Du
authors.affiliation: Hematology and Oncology Department, Shenzhen Children's Hospital , Shenzhen , China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen, China; China National Genebank-Shenzhen, BGI-Shenzhen, Shenzhen, China.
authors.forename: Xueyu
authors.initials: X
authors.lastname: Hong
authors.affiliation: BGI-Shenzhen, Shenzhen, China; China National Genebank-Shenzhen, BGI-Shenzhen, Shenzhen, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.affiliation: Hematology and Oncology Department, Shenzhen Children's Hospital , Shenzhen , China.
authors.forename: Feiqiu
authors.initials: F
authors.lastname: Wen
authors.affiliation: BGI-Shenzhen, Shenzhen, China; China National Genebank-Shenzhen, BGI-Shenzhen, Shenzhen, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: KingMed Diagnostics , Guangzhou , China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Pan
authors.affiliation: Hematology and Oncology Department, Shenzhen Children's Hospital , Shenzhen , China.
authors.forename: Changgang
authors.initials: C
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China; China National Genebank-Shenzhen, BGI-Shenzhen, Shenzhen, China; Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
keywords: IGH; acute B lymphoblast leukemia; clonal evolution; high throughput sequencing; minimal residual disease