Immune receptor repertoires in pediatric and adult acute myeloid leukemia
Abstract Background Acute myeloid leukemia (AML), caused by the abnormal proliferation of immature myeloid cells in the blood or bone marrow, is one of the most common hematologic malignancies. Currently, the interactions between malignant myeloid cells and the immune microenvironment, especially T...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-11-01
|
| Series: | Genome Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13073-019-0681-3 |
| _version_ | 1818217068740214784 |
|---|---|
| author | Jian Zhang Xihao Hu Jin Wang Avinash Das Sahu David Cohen Li Song Zhangyi Ouyang Jingyu Fan Binbin Wang Jingxin Fu Shengqing Gu Moshe Sade-Feldman Nir Hacohen Wuju Li Xiaomin Ying Bo Li X. Shirley Liu |
| author_facet | Jian Zhang Xihao Hu Jin Wang Avinash Das Sahu David Cohen Li Song Zhangyi Ouyang Jingyu Fan Binbin Wang Jingxin Fu Shengqing Gu Moshe Sade-Feldman Nir Hacohen Wuju Li Xiaomin Ying Bo Li X. Shirley Liu |
| author_sort | Jian Zhang |
| collection | DOAJ |
| description | Abstract Background Acute myeloid leukemia (AML), caused by the abnormal proliferation of immature myeloid cells in the blood or bone marrow, is one of the most common hematologic malignancies. Currently, the interactions between malignant myeloid cells and the immune microenvironment, especially T cells and B cells, remain poorly characterized. Methods In this study, we systematically analyzed the T cell receptor and B cell receptor (TCR and BCR) repertoires from the RNA-seq data of 145 pediatric and 151 adult AML samples as well as 73 non-tumor peripheral blood samples. Results We inferred over 225,000 complementarity-determining region 3 (CDR3) sequences in TCR α, β, γ, and δ chains and 1,210,000 CDR3 sequences in B cell immunoglobulin (Ig) heavy and light chains. We found higher clonal expansion of both T cells and B cells in the AML microenvironment and observed many differences between pediatric and adult AML. Most notably, adult AML samples have significantly higher level of B cell activation and more secondary Ig class switch events than pediatric AML or non-tumor samples. Furthermore, adult AML with highly expanded IgA2 B cells, which might represent an immunosuppressive microenvironment, are associated with regulatory T cells and worse overall survival. Conclusions Our comprehensive characterization of the AML immune receptor repertoires improved our understanding of T cell and B cell immunity in AML, which may provide insights into immunotherapies in hematological malignancies. |
| first_indexed | 2024-12-12T07:02:00Z |
| format | Article |
| id | doaj.art-451f73e2e69f431db98923ca1e3a0825 |
| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-12-12T07:02:00Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj.art-451f73e2e69f431db98923ca1e3a08252022-12-22T00:33:49ZengBMCGenome Medicine1756-994X2019-11-0111111110.1186/s13073-019-0681-3Immune receptor repertoires in pediatric and adult acute myeloid leukemiaJian Zhang0Xihao Hu1Jin Wang2Avinash Das Sahu3David Cohen4Li Song5Zhangyi Ouyang6Jingyu Fan7Binbin Wang8Jingxin Fu9Shengqing Gu10Moshe Sade-Feldman11Nir Hacohen12Wuju Li13Xiaomin Ying14Bo Li15X. Shirley Liu16Center for Computational Biology, Beijing Institute of Basic Medical SciencesDepartment of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public HealthDepartment of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public HealthDepartment of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public HealthDepartment of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public HealthDepartment of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public HealthDepartment of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public HealthDepartment of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public HealthDepartment of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public HealthDepartment of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public HealthDepartment of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public HealthMassachusetts General Hospital Cancer Center, Harvard Medical School (HMS)Massachusetts General Hospital Cancer Center, Harvard Medical School (HMS)Center for Computational Biology, Beijing Institute of Basic Medical SciencesCenter for Computational Biology, Beijing Institute of Basic Medical SciencesLyda Hill Department of Bioinformatics, UT Southwestern Medical CenterDepartment of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public HealthAbstract Background Acute myeloid leukemia (AML), caused by the abnormal proliferation of immature myeloid cells in the blood or bone marrow, is one of the most common hematologic malignancies. Currently, the interactions between malignant myeloid cells and the immune microenvironment, especially T cells and B cells, remain poorly characterized. Methods In this study, we systematically analyzed the T cell receptor and B cell receptor (TCR and BCR) repertoires from the RNA-seq data of 145 pediatric and 151 adult AML samples as well as 73 non-tumor peripheral blood samples. Results We inferred over 225,000 complementarity-determining region 3 (CDR3) sequences in TCR α, β, γ, and δ chains and 1,210,000 CDR3 sequences in B cell immunoglobulin (Ig) heavy and light chains. We found higher clonal expansion of both T cells and B cells in the AML microenvironment and observed many differences between pediatric and adult AML. Most notably, adult AML samples have significantly higher level of B cell activation and more secondary Ig class switch events than pediatric AML or non-tumor samples. Furthermore, adult AML with highly expanded IgA2 B cells, which might represent an immunosuppressive microenvironment, are associated with regulatory T cells and worse overall survival. Conclusions Our comprehensive characterization of the AML immune receptor repertoires improved our understanding of T cell and B cell immunity in AML, which may provide insights into immunotherapies in hematological malignancies.http://link.springer.com/article/10.1186/s13073-019-0681-3Acute myeloid leukemiaT cell receptor repertoiresB cell receptor repertoiresComplementarity-determining region 3 |
| spellingShingle | Jian Zhang Xihao Hu Jin Wang Avinash Das Sahu David Cohen Li Song Zhangyi Ouyang Jingyu Fan Binbin Wang Jingxin Fu Shengqing Gu Moshe Sade-Feldman Nir Hacohen Wuju Li Xiaomin Ying Bo Li X. Shirley Liu Immune receptor repertoires in pediatric and adult acute myeloid leukemia Genome Medicine Acute myeloid leukemia T cell receptor repertoires B cell receptor repertoires Complementarity-determining region 3 |
| title | Immune receptor repertoires in pediatric and adult acute myeloid leukemia |
| title_full | Immune receptor repertoires in pediatric and adult acute myeloid leukemia |
| title_fullStr | Immune receptor repertoires in pediatric and adult acute myeloid leukemia |
| title_full_unstemmed | Immune receptor repertoires in pediatric and adult acute myeloid leukemia |
| title_short | Immune receptor repertoires in pediatric and adult acute myeloid leukemia |
| title_sort | immune receptor repertoires in pediatric and adult acute myeloid leukemia |
| topic | Acute myeloid leukemia T cell receptor repertoires B cell receptor repertoires Complementarity-determining region 3 |
| url | http://link.springer.com/article/10.1186/s13073-019-0681-3 |
| work_keys_str_mv | AT jianzhang immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT xihaohu immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT jinwang immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT avinashdassahu immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT davidcohen immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT lisong immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT zhangyiouyang immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT jingyufan immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT binbinwang immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT jingxinfu immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT shengqinggu immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT moshesadefeldman immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT nirhacohen immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT wujuli immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT xiaominying immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT boli immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia AT xshirleyliu immunereceptorrepertoiresinpediatricandadultacutemyeloidleukemia |