AUTHOR=Li Xue-Ping , Song Jiang-Tao , Dai Yu-Ting , Zhang Wei-Na , Zhao Bai-Tian , Mao Jia-Ying , Gao Yan , Jiang Lu , Liang Yang 

TITLE=Integrative single-cell analysis of longitudinal t(8;21) AML reveals heterogeneous immune cell infiltration and prognostic signatures

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1424933

DOI=10.3389/fimmu.2024.1424933

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Immunotherapies targeting T cells in solid cancers are revolutionizing clinical treatment. Novel immunotherapies have had extremely limited benefit for acute myeloid leukemia (AML). Here, we characterized the immune microenvironment of t(8;21) AML patients to determine how immune cell infiltration status influenced prognosis.</p></sec><sec><title>Methods</title><p>Through multi-omics studies of primary and longitudinal t(8;21) AML samples, we characterized the heterogeneous immune cell infiltration in the tumor microenvironment and their immune checkpoint gene expression. Further external cohorts were also included in this research.</p></sec><sec><title>Results</title><p>CD8+ T cells were enriched and <italic>HAVCR2</italic> and <italic>TIGIT</italic> were upregulated in the CD34<sup>+</sup>CD117<sup>dim</sup>%-High group; these features are known to be associated with immune exhaustion. Data integration analysis of single-cell dynamics revealed that a subset of T cells (cluster_2) (highly expressing <italic>GZMB, NKG7, PRF1</italic> and <italic>GNLY</italic>) evolved and expanded markedly in the drug-resistant stage after relapse. External cohort analysis confirmed that the cluster_2 T-cell signature could be utilized to stratify patients by overall survival outcome.</p></sec><sec><title>Discussion</title><p>In conclusion, we discovered a distinct T-cell signature by scRNA-seq that was correlated with disease progression and drug resistance. Our research provides a novel system for classifying patients based on their immune microenvironment.</p></sec>