Identification of 9-O acetyl sialoglycoconjugates (9-OAcSGs) as biomarkers in childhood acute lymphoblastic leukemia using a lectin, AchatininH, as a probe

Leukemia. 1999 Jan;13(1):119-25. doi: 10.1038/sj.leu.2401239.

Abstract

Neoplastic transformation causes changes in cell surface architecture, most notably, aberrant sialylation. Exploiting the restricted specificity of a 9-O acetyl sialic acid (9-OAcSA) binding lectin, AchatininH (ATN(H)), we have identified two 9-O acetyl sialoglyconjugates (9-OAcSGs) on lymphoblasts of 87 children suffering from acute lymphoblastic leukemia (ALL). The preferential binding of ATN(H) to lymphoblasts induces their 11-fold increased agglutination (81 +/- 7.8%) compared to peripheral blood mononuclear cells (PBMC) of normal donors (8 +/- 4.3%) which corroborates with flow cytometry studies. Agglutination of MOLT-4 (87 +/- 4.8%), a lymphoblastoid cell line and MDCK (91.25 +/- 0.01%), a cell line expressing surface 9-OAcSA, confirms the preferential binding of ATN(H) to lymphoblasts through their surface 9-OAcSGs. Furthermore, fluorometric quantitation reveals a 4.6-fold increase in % of 9-OAcSA on lymphoblasts of ALL patients (42.1 +/- 4.1%) compared to normal donors (9.2 +/- 3.4%). Western blotting confirms that ATN(H) recognizes two membrane sialoglycoconjugates, of MW 120 kDa and 90 kDa, both having 9-OAcSA alpha2 --> 6 GalNAc terminal sugar moiety as their lectinogenic epitope. We propose that these 9-OAcSGs may serve as biomarkers for detection and monitoring of lymphoblasts in ALL and accordingly merit therapeutic considerations.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agglutination Tests / methods
  • Animals
  • Biomarkers, Tumor / blood*
  • Carbohydrate Sequence
  • Child
  • Disaccharides
  • Flow Cytometry / methods
  • Humans
  • Indicators and Reagents
  • Lectins*
  • Lymphocytes / cytology
  • Lymphocytes / pathology*
  • Molecular Sequence Data
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Reference Values
  • Sensitivity and Specificity
  • Sialoglycoproteins / blood*
  • Snails
  • Trisaccharides
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Disaccharides
  • Indicators and Reagents
  • Lectins
  • Sialoglycoproteins
  • Trisaccharides
  • achatinin(H)