AUTHOR=Sun Kai , Shi Zong-Yan , Wang Ya-Zhe , Xie Dai-Hong , Liu Yan-Rong , Jiang Qian , Jiang Hao , Huang Xiao-Jun , Qin Ya-Zhen 

TITLE=The profile and prognostic significance of bone marrow T-cell differentiation subsets in adult AML at diagnosis

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1418792

DOI=10.3389/fimmu.2024.1418792

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>T lymphocytes in tumor microenvironment play a pivotal role in the anti-tumor immunity, and the memory of T cells contributes to the long-term protection against tumor antigens. Compared to solid tumors, studies focusing on the T-cell differentiation in the acute myeloid leukemia (AML) bone marrow (BM) microenvironment remain limited.</p></sec><sec><title>Patients and methods</title><p>Fresh BM specimens collected from 103 adult AML patients at diagnosis and 12 healthy donors (HDs) were tested T-cell differentiation subsets by multi-parameter flow cytometry.</p></sec><sec><title>Results</title><p>CD4 and CD8 T-cell compartments had different constituted profiles of T-cell differentiated subsets, which was similar between AML patients and HDs. Compared to HDs, AML patients as a whole had a significantly higher proportion of CD8 effector T cells (Teff, <italic>P</italic> = 0.048). Moreover, the T-cell compartment of AML patients with no <italic>DNMT3A</italic> mutations skewed toward terminal differentiation at the expense of memory T cells (CD4 Teff: <italic>P</italic> = 0.034; CD8 Teff: <italic>P</italic> = 0.030; CD8 memory T: <italic>P</italic> = 0.017), whereas those with mutated <italic>DNMT3A</italic> had a decrease in CD8 naïve T (Tn) and CD4 effector memory T cells (Tem) as well as an increase in CD4 central memory T cells (Tcm) (<italic>P</italic> = 0.037, 0.053 and 0.053). Adverse ELN genetic risk correlated with a lower proportion of CD8 Tn. In addition, the low proportions of CD4 Tem and CD8 Tn independently predicted poorer relapse-free survival (RFS, HR [95%CI]: 5.7 (1.4–22.2), <italic>P</italic> = 0.017 and 4.8 [1.3–17.4], <italic>P</italic> = 0.013) and event-free survival (EFS, HR [95% CI]: 3.3 (1.1–9.5), <italic>P</italic> = 0.029; 4.0 (1.4–11.5), <italic>P</italic> = 0.010), respectively.</p></sec><sec><title>Conclusions</title><p>AML patients had abnormal profiles of BM T-cell differentiation subsets at diagnosis, which was related to <italic>DNMT3A</italic> mutations. The low proportions of CD4 Tem and CD8 Tn predicted poor outcomes.</p></sec>