Characteristics of the TCR Vβ repertoire in imatinib-resistant chronic myeloid leukemia patients with ABL mutations

作     者：XU Ling LU Yu Hong LAI Jing YU Wei ZHANG Yi Kai JIN Zhen Yi XU Yan CHEN Jie ZHA Xian Feng CHEN Shao Hua YANG Li Jian LI Yang Qiu 

作者机构：Institute of Hematology Jinan University Department of Hematology First Affiliated Hospital Jinan University Department of Hematology Guangzhou No.12 People's Hospital Key Laboratory for Regenerative Medicine of Ministry of Education Jinan University Department of clinical laboratory First Affiliated Hospital Jinan University 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2015年第58卷第12期

页      面：1276-1281页

核心收录：

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

基　　金：supported by the National Natural Science Foundation of China(81270604 U1301226 81400109) the China Postdoctoral Science Foundation(2013M540685) the Guangdong Natural Science Foundation(S2013040016151 S2013020012863) the Foundation for High-level Talents in Higher Education of Guangdong China(246-54) the Guangzhou Science and Technology Project Foundation(201510010211) Jinan University’s Scientific Research Creativeness Cultivation Project for Outstanding Undergraduates Recommended for Postgraduate Study 

主　　题：T cell repertoire chronic myeloid leukemia blast crisis imatinib resistance BCR-ABL mutation 

摘      要：Diversity in the T cell receptor(TCR) repertoire provides a miniature defense ability for the T cell immune system that may be related to tumor initiation and progression. Understanding the T cell immune status of leukemia patients is critical for establishing specific immunotherapies. Previous studies have reported abnormal TCR repertoires and clonally expanded TCR V? T cells in chronic myeloid leukemia in chronic phase(CP-CML). In this study, we investigated the distribution and clonality of the TCR V? repertoire in 4 cases with imatinib-resistant CML in blast crisis(BC-CML) with abelson murine leukemia viral oncogene homolog 1(ABL1) kinase domain mutations(KDMs). Examination of TCR V? expression and clonality was performed by reverse transcription-polymerase chain reaction(RT-PCR) and Gene Scan analysis. Significantly skewed TCR V? repertoires were observed in BC-CML patients with different KDMs, and 4 to 8 oligoclonally expanded TCR V? subfamilies could be identified in each sample. Intriguingly, a relatively highly expanded V?9 clone with the same length as complementarity-determining region 3(CDR3)(139 bp) was found in all three CML patients in lymphoid blast crisis(LBC-CML) who had different KDMs, but the clone was not detected in the only CML patient in myeloid blast crisis(MBC-CML). In conclusion, restricted TCR V? repertoire expression and decreased clone complexity was a general phenomenon observed in the BC-CML patients with different KDMs, indicating the T-cell immunodeficiency of these patients. In addition, clonally expanded V?9 T cell clones may indicate a specific immune response to leukemia-associated antigens in LBC-CML patients.