A Comparative Analysis of the Immunoglobulin Repertoire in Leukemia Cells and B Cells in Chinese Acute Myeloid Leukemia by High-Throughput Sequencing
Huige Yan,
Lina Wu,
Pingzhang Wang,
Miaoran Xia,
Zhan Shi,
Xinmei Huang,
Sha Yin,
Qian Jiang,
C. Cameron Yin,
Xiangyu Zhao,
Xiaoyan Qiu
Affiliations
Huige Yan
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
Lina Wu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Central Laboratory, Peking University Cancer Hospital & Institute, Beijing 100142, China
Pingzhang Wang
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
Miaoran Xia
Department of Immunology, Capital Medical University, Beijing 100069, China
Zhan Shi
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
Xinmei Huang
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
Sha Yin
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
Qian Jiang
Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University People’s Hospital, No. 11 South Street of Xizhimen, Xicheng District, Beijing 100044, China
C. Cameron Yin
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Xiangyu Zhao
Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University People’s Hospital, No. 11 South Street of Xizhimen, Xicheng District, Beijing 100044, China
Xiaoyan Qiu
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
It is common knowledge that immunoglobulin (Ig) is produced by B lymphocytes and mainly functions as an antibody. However, it has been shown recently that myeloblasts from acute myeloid leukemia (AML) could also express Ig and that AML-Ig played a role in leukemogenesis and AML progression. The difference between Ig from myeloblasts and B cells has not been explored. Studying the characteristics of the Ig repertoire in myeloblasts and B cells will be helpful to understand the function and significance of AML-Ig. We performed 5′ RACE-related PCR coupled with PacBio sequencing to analyze the Ig repertoire in myeloblasts and B cells from Chinese AML patients. Myeloblasts expressed all five classes of IgH, especially Igγ, with a high expression frequency. Compared with B-Ig in the same patient, AML-Ig showed different biased V(D)J usages and mutation patterns. In addition, the CDR3 length distribution of AML-Ig was significantly different from those of B-Ig. More importantly, mutations of AML-IgH, especially Igμ, Igα, and Igδ, were different from that of B-IgH in each AML patient, and the mutations frequently occurred at the sites of post-translational modification. AML-Ig has distinct characteristics of variable regions and mutations, which may have implications for disease monitoring and personalized therapy.
