Identification of 9-O acetyl sialoglycoconjugates (9-OAcSGs) as biomarkers in childhood acute lymphoblastic leukemia using a lectin, AchatininH, as a probe.
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.
Indian Institute of Chemical Biology, Calcutta.
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Sinha
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Mandal
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Bhattacharya
D000372:Agglutination Tests / Q000379:methods; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D002240:Carbohydrate Sequence; D002648:Child; D004187:Disaccharides; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007202:Indicators and Reagents; D037102:Lectins; D008214:Lymphocytes / Q000166:cytology / Q000473:pathology*; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000175:diagnosis*; D012016:Reference Values; D012680:Sensitivity and Specificity; D012795:Sialoglycoproteins / Q000097:blood*; D012908:Snails; D014312:Trisaccharides; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D004187:Disaccharides; D007202:Indicators and Reagents; D037102:Lectins; D012795:Sialoglycoproteins; D014312:Trisaccharides; C050704:achatinin(H)