Th17 cells and interleukin-17 increase with poor prognosis in patients with acute myeloid leukemia.
Bottom Line: In addition, combination of IL-17A and IL-22 significantly reduced the generation of Th1 cells and the production of interferon (IFN)-γ from healthy donor or AML patient peripheral blood mononuclear cells.Patients with high Th17 cell frequency had poor prognosis, whereas patients with high Th1 cell frequency had prolonged survival.Combined analysis of Th1 and Th17 cell frequencies improved the ability to predict patient outcomes.
Affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.Show MeSH
Related in: MedlinePlus
Mentions: After showing elevated existence of Th17 cells in BM from AML patients, we next investigated whether IL-17A, a signature cytokine secreted by Th17 cells, has any effects on AML cells. First, we assessed the proliferation of AML cells in the presence or absence of IL-17A. As shown in Figure 4(a), 50 ng/mL IL-17A only exhibited an increase in the proliferation of U937 as well as primary AML cells, but not in HL-60 and Dami cells. After treatment with IL-17A for 7 days, S phase cells of U937 and primary AML cells, although increased, were not statistically significant compared with control (P > 0.05, Fig. S1). IL-17A had also no significant effect on the induction of apoptosis (Fig. S2). IL-17R has been found to be ubiquitously expressed in many tissues and cell types.(25) We further investigated whether the IL-17R expression associates with IL-17-induced proliferation. Abundant expression of IL-17RA was present in U937 cells as well as most primary AML cells, but only weak expression in HL-60 and Dami cells (Fig. 4b), which was further confirmed by measuring the relative expression of IL-17R mRNA (Fig. S3). A positive correlation between IL-17A-induced proliferation and the IL-17RA expression was observed in primary AML cells (Fig. 4c). Therefore, we determined the role of IL-17R in IL-17A-induced AML cell proliferation using anti-IL-17R antibody. As shown in Figure 4(d), anti-IL-17R antibody significantly inhibited AML cell proliferation in the presence of IL-17A.
Affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.