Circulating Monocytic Myeloid-Derived Suppressor Cells Are Elevated and Associated with Poor Prognosis in Acute Myeloid Leukemia

Abstract

Background. Monocytic myeloid-derived suppressor cells (M-MDSCs) characterized with the phenotype of CD14+HLA-DRlow/- have attracted a lot of attention in the field of human tumor immunology. However, little is known about the roles of M-MDSCs in acute myeloid leukemia (AML) as opposed to their multiple roles in solid tumors. Methods. We examined the frequencies of M-MDSCs identified for CD14+HLA-DRlow/- by flow cytometry in the peripheral circulating blood of 109 newly diagnosed adult patients with AML and 30 healthy controls (HC). Then, we, respectively, validated the clinic significance of circulating M-MDSCs on the relevance of spectral features for diagnostic stratification, induction therapy response, treatment effect maintenance, and long-term survival in AML. Results. Circulating M-MDSC frequencies of AML were significantly higher than those of HC both in CD14+ monocytes ( $46.22\%\pm 2.95\%$ vs. $1.07\%\pm 0.17\%$ , $p<0.01$ ) and peripheral blood mononuclear cells (PBMCs) ( $4.21\%\pm 0.80\%$ vs. $0.17\%\pm 0.03\%$ , $p<0.01$ ). Elevated circulating M-MDSCs in patients with AML were significantly associated with low complete remission (CR) rate, high relapse/refractory rate, and poor long-term survival, but had no correlation with common clinic risks and cytogenetic molecular risk categories. Conclusions. It was demonstrated that circulating M-MDSCs are elevated and associated with poor prognosis in AML, suggesting M-MDSCs might be a prognostic indicator for AML.