title: Azacitidine differentially affects CD4(pos) T-cell polarization in vitro and in vivo in high risk myelodysplastic syndromes.
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.
authors.affiliation: Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. hj.bontkes@vumc.nl
authors.forename: Hetty J
authors.initials: HJ
authors.lastname: Bontkes
authors.forename: Jurjen M
authors.initials: JM
authors.lastname: Ruben
authors.forename: Canan
authors.initials: C
authors.lastname: Alhan
authors.forename: Theresia M
authors.initials: TM
authors.lastname: Westers
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: Arjan A
authors.initials: AA
authors.lastname: van de Loosdrecht
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology*; D017252:CD3 Complex / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D016764:Cell Polarity / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000276:immunology / Q000473:pathology*; D009367:Neoplasm Staging; D012306:Risk
chemical_list: D000964:Antimetabolites, Antineoplastic; D017252:CD3 Complex; D016207:Cytokines; D001374:Azacitidine