Clonal evolution analyses of a chronic myeloid leukemia patient with hematopoietic stem cell transplantation based on deep sequencing

作     者：Fuhua Yang Ping Wang Jia Wan Xiaoqing Jia An Zhou Yuan Zhang Jiani Song Qiang Gong Wei-Dong Li Jieping Chen 

作者机构：Department of GeneticsSchool of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Tianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China Department of HematologySouthwest HospitalArmy Medical UniversityChongqing 400038China 

出 版 物：《Holistic Integrative Oncology》 (整合肿瘤学（英文）)

年 卷 期：2023年第2卷第1期

页      面：85-92页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported in part by National Key R&D Program of China(2017YFC1001903) National Natural Science Foundation of China(NSFC 39870046,81270605,30971066,81470324)to J.C National Natural Science Foundation of China(92046014) Beijing-Tianjin-Hebei Jointed Research Program(19JCZDJC64700)to W-D.L 

主　　题：Philadelphia chromosome Clonal evolution DNA repair Homologous recombination Targeted therapy 

摘      要：Background The Philadelphia(Ph)chromosome is the hallmark chromosome aberration in chronic myeloid leukemia(CML),which confers the cancer phenotype of the ***,how the Ph chromosome forms and the genetic clonal evolution structure after targeted Ph treatment are still *** In this study,we performed genome sequencing and clonal evolution analyses in a series of bone marrow specimens and skin biopsy from a CML patient who had received hematopoietic stem cell transplantation from her sister,then relapsed(lymphoid blast crisis),and received Ph-targeted *** The Ph chromosome was the“driverclonal change in the original CML and the *** the patient and her sister had micro-deletions in the BCR gene region;however,the patient had a frameshift BRIP1 mutation that may account for the malfunctioning homologous recombination DNA repair of the BCR gene region and formation of the Ph *** We found that the BCR-ABL1 translocation was the driving force of the patient’s CML and *** malfunctioning double-strand DNA break repair caused by the BRIP1 mutation could be the cause of Ph chromosome formation in the patient.