Up-regulation of regulatory T cells, CD200 and TIM3 expression in cytogenetically normal acute myeloid leukemia

Cancer Biomark. 2018;22(3):587-595. doi: 10.3233/CBM-181368.

Abstract

Background: The bone marrow immunosuppressive microenvironment of AML patients sustains and modulates proliferation, survival and drug resistance of AML through deregulation of both innate and adaptive immune response. We aimed to investigate the level of Tregs, expression of Tim-3 on peripheral blood T cells, expression of CD200 in myeloid blasts in newly diagnosed AML patients with normal cytogenetics (AML-NC) and their prognostic impact.

Patients and methods: This study included 40 patients with de novo AML-NC and 20 healthy controls. Flow-cytometry was used for detection of CD4+CD25+high FoxP3+ regulatory T cells, Tim-3 expression on peripheral blood T cells and CD200 expression on myeloid blasts.

Results: The percentages of CD4+CD25+high and CD4+CD25+high Foxp3+ Tregs were significantly increased in AML patients than controls. The levels of Tregs, Tim-3/CD4+, Tim-3/CD8+, CD200 and MFI of CD200 were significantly lower in responding patients than in those with persistent leukemia. Only high CD200 expression (> 50%) showed statistically significant worse OS with P< 0.04.

Conclusion: The increased levels of Tregs, Tim-3 expression on peripheral blood T cells and CD200 expression in myeloid blast in AML patients could play a role in the development of AML. Analysis of these markers could serve as prognostic markers and might guide the therapy in AML patients in the future.

Keywords: CD200; Regulatory T cells; TIM3; acute myeloid leukemia; normal cytogenetics.

MeSH terms

  • Adult
  • Antigens, CD / metabolism*
  • Biomarkers, Tumor
  • Bone Marrow / pathology
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Case-Control Studies
  • Cytogenetic Analysis
  • Female
  • Flow Cytometry
  • Gene Expression
  • Hepatitis A Virus Cellular Receptor 2 / metabolism*
  • Humans
  • Immunophenotyping
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / etiology
  • Leukemia, Myeloid, Acute / metabolism*
  • Leukemia, Myeloid, Acute / mortality
  • Lymphocyte Count
  • Male
  • Prognosis
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • antigens, CD200