Elevated Circulating CD10¯ G-MDSC-like Neutrophils of Acute Myeloid Leukemia Patients in Complete Remission Status Are Correlated with Relapse and Poor Prognosis

Objectives: To explore the level of circulating granulocytic myeloid-derived suppressor cell-like (G-MDSC-like) neutrophils with CD10^-CD14^-CD45⁺HLA-DR^-SSC⁺⁺ immunophenotype in acute myeloid leukemia (AML) patients of complete remission (CR) status and whether it is associated with relapse and poor prognosis. Methods: 90 AML patients in CR status and 60 healthy controls (HCs) were enrolled in this study. The levels of CD10^-CD14^-CD45⁺HLA-DR^-SSC⁺⁺ neutrophils (CD10^- neuts) in peripheral blood of AML patients in CR status were detected by flow cytometry (FCM) at the time when AML patients reached the first CR after induction chemotherapy. The levels of CD10^- neuts were reflected with three indicators, including the frequency of CD10^- neuts accounted for neutrophils (CD10^- neuts/neutrophils), frequency of CD10^- neuts accounted for nucleated cells (CD10^- neuts/nucleated cells) and absolute count of CD10^- neuts (CD10^- neuts count). The correlation between the three aforementioned indicators and both relapsse-free survival (RFS) and overall survival (OS) is further examined. To preliminarily explore possible mechanisms of CD10^- neuts related to prognosis, T cells from patients were isolated and cultured alone or co-cultured with autologous CD10^- neuts or CD10⁺ neutrophils for 24 or 48h, and the proliferation and apoptosis of CD3⁺T, CD4⁺T, and CD8⁺T cells were detected. Results: CD10^- neuts/neutrophils, CD10^- neuts/nucleated cells, and CD10^- neuts count in CR AML patients were all higher than HCs (6.28% vs 3.65%, 2.33% vs 1.74%, 105.1/uL vs 95.14/uL, all p < 0.05). CD10^- neuts/neutrophils, CD10^- neuts/nucleated cells, and CD10^- neuts count (8.03% vs 4.72%, 2.94% vs 1.67%, 153.40/uL vs 71.22/uL, p < 0.01) of patients with medium-high risk molecular genetics were significant higher than patients with low risk. Patients with positive bone marrow minimal residual disease (BM-MRD) measured by FCM had higher CD10^- neuts/neutrophils, CD10^- neuts/nucleated cells, CD10^- neuts count than those with negative BM-MRD (19.31% vs 5.85%, 5.0% vs 2.15%, 153.40/uL vs 71.22/uL, p < 0.01). ROC curves found that CD10^- neuts/neutrophils, CD10^- neuts/nucleated cells and CD10^- neuts count(19.31% vs 5.85%, 5.0% vs 2.15%, 153.40/uL vs 71.22/uL, p < 0.01) all have prediction on relapse. Cut-off value were determined by ROC curves. The median RFS of high CD10^- neuts/neutrophils(≥15.02%) was shorter than the low CD10^- neuts/neutrophils (13.3 months vs not reached, p < 0.001). The median RFS of high CD10^- neuts/nucleated cells (≥4.77%) and high CD10^- neuts count (≥271.5/uL) were also shorter than the low CD10^- neuts/nucleated cells and CD10^- neuts count (p < 0.01). Similarly, the median OS of high CD10^- neuts/neutrophils and CD10^- neuts/nucleated cells were shorter than low CD10^- neuts/neutrophils and CD10^- neuts/nucleated cells, respectively. In addition, high CD10^- neuts/neutrophils was an independent risk factor for RFS and OS (HR = 14.02, p = 0.003; HR = 22.06, p = 0.005). CD10^- neuts from patients inhibited T cell proliferation and increased T cell apoptosis in the co-culture system in vitro, especially increased CD8⁺T cell apoptosis. Conclusions: Elevated circulating CD10^- neuts of AML patients can be a potential indicator to predict early relapse and poor prognosis after achieving CR, and may be one mechanism that leads to AML relapse through inhibiting T cell function.