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Purification and characterization of 9-O-acetylated sialoglycoproteins from leukemic cells and their potential as immunological tool for monitoring childhood acute lymphoblastic leukemia

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Title Purification and characterization of 9-O-acetylated sialoglycoproteins from leukemic
cells and their potential as immunological tool for monitoring childhood acute
lymphoblastic leukemia
 
Creator Pal, Santanu
Ghosh, Shyamasree
Mandal, Chhabinath
Kohla, Guido
Brossmer, Reinhard
Isecke, Rainer
Merling, Anette
Schauer, Roland
Schwartz-Albiez, Reinhard
Bhattacharya, Dilip K
Mandal, Chitra
 
Subject Infectious Diseases and Immunology
 
Description Sialic acids as terminal residues of oligosaccharide chains play
crucial roles in several cellular recognition events. Exploiting
the selective affinity of Achatinin-H toward N-acetyl-9-Oacetylneuraminic
acid-a2-6-GalNAc, we have demonstrated
the presence of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-
GPs) on lymphoblasts of 70 children with acute lymphoblastic
leukemia (ALL) and on leukemic cell lines by fluorimetric
HPLC and flow cytometric analysis. This study aims to assess
the structural aspect of the glycotope of Neu5,9Ac2-GPsALL
and to evaluate whether these disease-specific molecules can be
used to monitor the clinical outcome of ALL. The Neu5,9Ac2-
GPsALL were affinity-purified, and three distinct leukemiaspecific
molecular determinants (135, 120, and 90 kDa) were
demonstrated bySDS–PAGE, western blotting, and isoelectric
focusing. The carbohydrate epitope of Neu5,9Ac2-GPsALL was
confirmed by using synthetic sialic acid analogs. The enhanced
presence of anti-Neu5,9Ac2-GPALL antibody in ALL patients
prompted us to develop an antigen-ELISA using purified
Neu5,9Ac2-GPsALL as coating antigens. Purified antigen was
able to detect leukemia-specific antibodies at presentation of
disease, which gradually decreased with treatment. Longitudinal
monitoring of 18 patients revealed that in the early phase of
the treatment patients with lower anti-Neu5,9Ac2-GPs showed
a better prognosis. Minimal cross-reactivity was observed in
other hematological disorders (n¼50) like chronic myeloid leukemia, acute myelogenous leukemia, chronic lymphocytic
leukemia, and non-Hodgkin’s lymphoma as well as normal
healthy individuals (n¼21). This study demonstrated the
potential of purified Neu5,9Ac2-GPsALL as an alternate tool
for detection of anti-Neu5,9Ac2-GP antibodies to be helpful for
diagnosis and monitoring of childhood ALL patients.
 
Publisher Oxford University Press
 
Date 2004
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/524/1/GLYCOBIOLOGY%2C__14(_10)%2C_859%2D870_[17].pdf
Pal, Santanu and Ghosh, Shyamasree and Mandal, Chhabinath and Kohla, Guido and Brossmer, Reinhard and Isecke, Rainer and Merling, Anette and Schauer, Roland and Schwartz-Albiez, Reinhard and Bhattacharya, Dilip K and Mandal, Chitra (2004) Purification and characterization of 9-O-acetylated sialoglycoproteins from leukemic cells and their potential as immunological tool for monitoring childhood acute lymphoblastic leukemia. Glycobiology, 14 (10). pp. 859-870.
 
Relation http://dx.doi.org/10.1093/glycob/cwh111
http://www.eprints.iicb.res.in/524/