Activation of HLA-G expression by 5-aza-2 - deoxycytidine in malignant hematopoetic cells isolated from leukemia patients

Neoplasma. 2009;56(6):514-20. doi: 10.4149/neo_2009_06_514.

Abstract

Human leukocyte antigen - G (HLA-G) is a non-classical HLA class I antigen with restricted distribution in normal tissues. Ectopic HLA-G expression observed at some pathological circumstances as malignant transformation might be triggered by epigenetic modifications such as DNA demethylation. Recently it was demonstrated that DNA methyltransferase inhibitor 5-aza-2 - deoxycytidine (AdC) induces/enhances HLA-G transcription in many leukemia cell lines of different origin. Here we investigated the effect of AdC on HLA-G expression in malignant hematopoetic cells isolated from patients with acute myeloid leukemia (AML) and chronic lymphocytic leukemia (B-CLL). We detected HLA-G expression in untreated cells from some patients. Nevertheless treatment with 5-aza-2 - deoxycytidine enhanced HLA-G transcription and concomitantly HLA-G protein synthesis in some leukemia cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Blotting, Western
  • DNA Methylation
  • DNA Modification Methylases / antagonists & inhibitors
  • Decitabine
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Leukemic / drug effects*
  • HLA Antigens / genetics
  • HLA Antigens / metabolism*
  • HLA-G Antigens
  • Hematopoietic Stem Cells / pathology*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / metabolism*
  • Leukemia, Myeloid, Acute / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cell Transplantation

Substances

  • Antimetabolites, Antineoplastic
  • Enzyme Inhibitors
  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • RNA, Messenger
  • Decitabine
  • DNA Modification Methylases
  • Azacitidine