Increased interferon gamma production by peripheral blood mononuclear cells in response to stimulation of overexpressed disease-specific 9-O-acetylated sialoglycoconjugates in children suffering from acute lymphoblastic leukaemia

Br J Haematol. 2005 Jan;128(1):35-41. doi: 10.1111/j.1365-2141.2004.05256.x.

Abstract

Disease-specific over-expression of 9-O-acetylated sialoglycoconjugates (9-O-AcSGs) on peripheral blood mononuclear cells (PBMC) of children with acute lymphoblastic leukaemia (ALL, PBMC(ALL)) has been demonstrated using a lectin, Achatinin-H, with specificity towards 9-O-AcSAalpha2-6GalNAc. This study investigated the contributory role of 9-O-AcSGs induced on PBMC(ALL). Stimulation of PBMC(ALL) with Achatinin-H through 9-O-AcSGs led to a lymphoproliferative response with a significantly increased interferon-gamma (IFN-gamma) production when compared with unstimulated cells as demonstrated by enzyme-linked immunosorbent assay and mRNA expression. Under identical conditions, PBMC(ALL) ablated of O-acetylations did not respond to such stimulation. In summary, it may be concluded that stimulation of over-expressed 9-O-AcSGs regulate signalling for proliferation, leading to the release of IFN-gamma. Controlled expression of these molecules may be exploited as potential targets for therapy, promising beneficial effects to children with ALL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Flow Cytometry
  • Glycoconjugates / genetics
  • Glycoconjugates / metabolism*
  • Humans
  • Infant
  • Interferon-gamma / immunology*
  • Lectins / metabolism
  • Leukocytes, Mononuclear / chemistry*
  • Leukocytes, Mononuclear / immunology
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialic Acids / genetics
  • Sialic Acids / metabolism*
  • Signal Transduction / physiology
  • Stimulation, Chemical

Substances

  • Glycoconjugates
  • Lectins
  • RNA, Messenger
  • Sialic Acids
  • achatinin(H)
  • 9-O-acetyl-N-acetylneuraminic acid
  • Interferon-gamma