The imbalanced profile and clinical significance of T helper associated cytokines in bone marrow microenvironment of the patients with acute myeloid leukemia

Abstract

Background: Immunological disorder has shown to be related to the pathogenesis of acute myeloid leukemia (AML). The microenvironment of AML is immunosuppressive, favoring the survival of malignant hematopoietic cells. However, the systematic research on AML abnormal immune microenvironment, especially the T helper (Th) cells imbalance, remains unsettled.

Design and methods: The levels of cytokines in bone marrow plasma including Th1-associated cytokine (IFN-γ), Th2-associated cytokine (IL-4), Th17-associated cytokines (IL-17, IL-6, TGF-β, and IL-21), regulatory T cell (Treg)-associated cytokines (IL-35 and IL-10) and Th22-associated cytokine (IL-22) were examined by enzyme-linked immunosorbent assay (ELISA) in AML patients and controls. The relative expression levels of IL-4, IL-10, and IL-21 mRNA were analyzed by real time polymerase chain reaction (PCR).

Results: Significant differences on cytokine levels tested were observed among the AML newly-diagnosed (ND) patients, AML patients in complete remission (CR) and controls except IL-21 and IL-35. In AML-ND group IFN-γ level was positively correlated with IL-21 or IL-22 level. Additionally, significant associations were observed between IL-17, IL-21 and some clinical characteristics.

Conclusion: Our results showed that many cytokines were abnormal in AML bone marrow microenvironment. The dysregulation of Th subsets cytokines is thought to contribute to the pathogenesis of AML.

Keywords: AML; AMML; AMoL; APL; BM; CR; Ca; EL; ELISA; Hb; LDH; LYM; ND; NEU; PB; PLT; RT-PCR; T helper type 1; Th1; Treg; WBC; acute monocytic leukemia; acute myeloid leukemia; acute myelomonocytic leukemia; acute promyelocytic leukemia; bone marrow; calcium; complete remission; enzyme-linked immunosorbent assay; erythroleukemia; hemoglobin; lactate dehydrogenase; lymphocyte; neutrophil; newly diagnosed; peripheral blood; platelet; real time polymerase chain reaction; regulatory T cell; white blood cell count.