Azacitidine differentially affects CD4(pos) T-cell polarization in vitro and in vivo in high risk myelodysplastic syndromes

Leuk Res. 2012 Jul;36(7):921-30. doi: 10.1016/j.leukres.2012.03.026. Epub 2012 Apr 14.

Abstract

CD4(pos) T-cell subsets play a role in myelodysplastic syndromes (MDS) pathogenesis and may be affected upon 5-azacitidine (Aza) treatment. Aza enhanced human T(H)1 frequencies in vitro but not in vivo. The proportion of functional FoxP3(pos) regulatory T cells (Treg) was enhanced by Aza in vitro (p < 0.0002), and a modest, temporary increase was observed in vivo (p = 0.08). The overall number of T(H)17 was reduced both in vitro (p < 0.03) and in vivo (p < 0.006), indicating that Aza directly affects CD4(pos) polarization during activation in vitro. Upon in vivo treatment in high risk MDS patients, particularly the T(H)17-Treg axis is affected.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / pharmacology
  • Azacitidine / pharmacology*
  • CD3 Complex / metabolism
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology*
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Polarity / drug effects*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / metabolism
  • Humans
  • Myelodysplastic Syndromes / blood
  • Myelodysplastic Syndromes / immunology
  • Myelodysplastic Syndromes / pathology*
  • Neoplasm Staging
  • Risk

Substances

  • Antimetabolites, Antineoplastic
  • CD3 Complex
  • Cytokines
  • Azacitidine