Application and clinical significance of intercellular proximity labeling technique in chronic myelogenous leukemia
10.3760/cma.j.issn.0253-2727.2023.07.003
- VernacularTitle:细胞间邻近标记技术在慢性髓性白血病中的应用及其临床意义
- Author:
Lanlan AI
1
;
Anli LAI
;
Xiaohuan QIN
;
Bingcheng LIU
;
Jie LI
;
Jianxiang WANG
;
Ping ZHU
Author Information
1. 中国医学科学院血液病医院(中国医学科学院血液学研究所)、北京协和医学院,实验血液学国家重点实验室,国家血液系统疾病临床医学研究中心,细胞生态海河实验室,天津 300020
- Keywords:
Biochemical proximity labeling technology;
Hematological malignancy;
Leukemia myeloid, chronic;
Tumor antigen-specific T cell;
Immunophenotype
- From:
Chinese Journal of Hematology
2023;44(7):543-549
- CountryChina
- Language:Chinese
-
Abstract:
Objective:This study aimed to explore the application of interaction-dependent fucosyl-biotinylation (FucoID), a chemical biology-based proximity labeling technique, in capturing tumor antigen-specific T cells and its clinical value in chronic myelogenous leukemia (CML) .Methods:Flow cytometry and fluorescence microscopy were employed to evaluate the experimental parameters for FucoID in CML. Peripheral blood samples were obtained from 14 newly diagnosed CML patients in the chronic phase. These samples underwent flow cytometry-based sorting and were subsequently labeled with FucoID to facilitate the isolation of tumor cells and T cells, followed by the immunophenotypic identification of tumor antigen-specific T cells. Finally, the diagnostic and therapeutic potential of FucoID in CML was assessed.Results:Initially, the experimental parameters for FucoID in CML were established. The proportion of CD3 + T cells in patients was (8.96±6.47) %, exhibiting a marked decrease compared with that in healthy individuals at (38.89±22.62) %. The proportion of tumor-specific antigen-reactive T cells was (3.34±4.49) %, which demonstrated interpatient variability. In addition, the proportion of tumor-specific antigen-active T cells in CD4 + T cells was (3.95±1.72) %, which was generally lower than the proportion in CD8 + T cells at (5.68±2.18) %. Compared with those in tumor-specific antigen-nonreactive T cells, CCR7 -CD45RA - effector memory T cells and CCR7 -CD45RA + effector T cells were highly enriched in tumor-specific antigen-reactive T cells. Moreover, the intensity of tumor immune reactivity in patients exhibited a significant correlation with white blood cell count (WBC) and hemoglobin (HGB) levels in peripheral blood, while no such correlation was observed with other clinical baseline characteristics. Conclusion:The combination of FucoID and flow cytometry enables the rapid identification and isolation of tumor antigen-specific T cells in CML. The successful application of this method in CML and the implications of our findings suggest its potential clinical value in the field of hematologic malignancies.