title: Characteristics of the TCR Vβ repertoire in imatinib-resistant chronic myeloid leukemia patients with ABL mutations.
abstract: 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 Vβ T cells in chronic myeloid leukemia in chronic phase (CP-CML). In this study, we investigated the distribution and clonality of the TCR Vβ 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 GeneScan analysis. Significantly skewed TCR Vβ repertoires were observed in BC-CML patients with different KDMs, and 4 to 8 oligoclonally expanded TCR Vβ subfamilies could be identified in each sample. Intriguingly, a relatively highly expanded Vβ9 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 Vβ 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 Vβ9 T cell clones may indicate a specific immune response to leukemia-associated antigens in LBC-CML patients.
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.
authors.forename: YuHong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China.|Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lai
authors.affiliation: Department of Hematology, Guangzhou No.12 People's Hospital, Guangzhou, 510632, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China.
authors.forename: YiKai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China.
authors.forename: ZhenYi
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China.|Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of clinical laboratory, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.
authors.forename: XianFeng
authors.initials: X
authors.lastname: Zha
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China.
authors.forename: ShaoHua
authors.initials: S
authors.lastname: Chen
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China.
authors.forename: LiJian
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, 510632, China. yangqiuli@hotmail.com.|Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, China. yangqiuli@hotmail.com.|Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China. yangqiuli@hotmail.com.
authors.forename: YangQiu
authors.initials: Y
authors.lastname: Li
mesh_terms: D001752:Blast Crisis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D002999:Clone Cells / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D014644:Genetic Variation; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000068877:Imatinib Mesylate; D016315:Proto-Oncogene Proteins c-abl
keywords: BCR-ABL mutation; T cell repertoire; blast crisis; chronic myeloid leukemia; imatinib resistance