Abstract
In this study, we mainly investigate the role of Th17 cells, Th1 cells, and their related cytokines in the pathophysiology of AML. BM and PB were extracted from ND, CR, and relapsed-refractory AML patients and controls. Th subsets frequencies were examined by flow cytometry. BM plasma Th-associated cytokines levels were determined by ELISA. The frequencies of Th17 and Th1, and IFN-γ or TGF-β concentrations were significantly decreased in ND compared with CR patients or controls. Th17 percentage was significantly lower in BM than in PB for ND patients but was higher in BM for CR patients. However, in CR or relapsed-refractory patients, Th1 percentage in BM was higher than that in PB. Moreover, BM IL-17A level showed a decreased trend in ND patients. A significant elevation of plasma IL-6 level was found in ND compared with CR patients or controls. IL-17A showed the positive correlation with IL-6 concentration. And Th17 cells frequencies and TGF-β1 concentration were increased in BM from AML patients achieving CR after chemotherapy. Moreover, a significant decrease of BM plasma TGF-β1 level was found in M3 patients compared with the other subtypes. Our findings suggest that Th17 and related cytokines may be implicated in AML pathogenesis.
Highlights
Acute myeloid leukemia (AML) is a life-threatening hematopoietic stem cell neoplasm characterized by increased number of myeloid cells in the bone marrow and an arrest in their maturation, frequently resulting in fatal infection, bleeding, or organ infiltration, with or without leukocytosis [1,2,3]
In different stages of AML, Th17 cells frequencies were statistically decreased in newly diagnosed (ND) patients (1.76 ± 0.96%) compared to complete remission (CR) (5.082 ± 2.4%; ∗∗∗P < 0.0001) or relapsed-refractory AML patients (3.97 ± 2.17%; ∗P = 0.0011) or controls (3.63 ± 1.37%; ∗∗∗P < 0.0001) (Figure 2(a))
We firstly observed that aberrant Th17 or Th1 subset and associated cytokines in bone marrow (BM) microenvironment are involved in AML pathogenesis, and chemotherapy partly ameliorates this turmoil
Summary
Acute myeloid leukemia (AML) is a life-threatening hematopoietic stem cell neoplasm characterized by increased number of myeloid cells in the bone marrow and an arrest in their maturation, frequently resulting in fatal infection, bleeding, or organ infiltration, with or without leukocytosis [1,2,3]. The differentiation of Th17 cells is driven primarily by the cytokines transforming growth factor- (TGF-) β and IL-6, and it is known that IL-23 is necessary for the pathogenicity of Th17 cells [5, 8,9,10]. Retinoic acid-related orphan nuclear receptor gamma t (ROR-γt) is a transcription factor that is considered to be important for the initiation and maintenance of Th17 cell lineage [11, 12] and regulating the differentiation of Th17 subset. Volpe et al [13] have reported that TGF-β, IL-23, and proinflammatory cytokines (IL-1β and IL-6) were all essential for human Th17 differentiation. Acosta-Rodriguez et al [14] found that for human naive CD4+ T cells, ROR-γt expression and Th17 polarization were induced by IL-1β and enhanced by IL-6 but were suppressed by TGF-β and IL-12
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