Immune receptor repertoires in pediatric and adult acute myeloid leukemia

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 δchains 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.

Original languageEnglish (US)
Article number73
JournalGenome Medicine
Volume11
Issue number1
DOIs
StatePublished - Nov 26 2019

Keywords

  • Acute myeloid leukemia
  • B cell receptor repertoires
  • Complementarity-determining region 3
  • T cell receptor repertoires

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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