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Regulation of O-Acetylation of Sialic Acids by Sialate-O-Acetyltransferase and Sialate-O-Acetylesterase Activities in Childhood Acute Lymphoblastic Leukemia

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Title Regulation of O-Acetylation of Sialic Acids
by Sialate-O-Acetyltransferase and Sialate-O-Acetylesterase
Activities in Childhood Acute Lymphoblastic Leukemia
 
Creator Mandal, Chandan
Mandal, Chhabinath
Chandra, Sarmila
Schauer, Roland
Mandal, Chitra
 
Subject Cancer Biology and Inflammatory Disorder Division
 
Description Enhanced expression of 9-O-acetylated sialoglycoproteins
(Neu5,9Ac2-GPs) and 9-O-acetylated disialoganglioside
(9-OAcGD3) was observed on lymphoblasts of childhood
acute lymphoblastic leukemia (ALL). Sialate-O-acetyltransferase
(SOAT) and sialate-O-acetylesterase (SIAE)
are the two main enzymes responsible for the quantity of
the O-acetyl ester groups on sialic acids (Sias). We have
earlier shown an enhanced level of SOAT activity, capable
of transferring acetyl groups to Sias of glycoconjugates in
the microsomes of lymphoblasts of these children. We
further observed a decreased SIAE activity in both lysosomal
and cytosolic fractions of ALL cell lines and primary
cells from bone marrow of patients compared with peripheral
blood mononuclear cells from healthy donors, which
preferentially hydrolyze O-acetyl groups at C-9 of Sia. The
level of O-acetylated Sias in the cytosolic and the lysosomal
fractions showed a good correlation with SIAE
activity in the corresponding fractions. The apparent KM
values for SIAE in the lysosomal and the cytosolic fractions
from lymphoblasts of ALL patients are 0.38 and
0.39 mM, respectively. These studies demonstrate that
both SIAE and SOAT activities seem to be responsible for
the enhanced level of Neu5,9Ac2 in lymphoblasts, which is
a hallmark in ALL. This was subsequently confirmed by
using an enzyme-linked immunosorbent assay that also
demonstrated a steady decline in SOAT activities even in
cell lysates of lymphoblasts during successful chemotherapy,
like radioactive methods have shown earlier.
 
Publisher Oxford University Press
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1565/1/GLYCOBIOLOGY___22(_1)_70%2D83;2012[96].pdf
Mandal, Chandan and Mandal, Chhabinath and Chandra, Sarmila and Schauer, Roland and Mandal, Chitra (2012) Regulation of O-Acetylation of Sialic Acids by Sialate-O-Acetyltransferase and Sialate-O-Acetylesterase Activities in Childhood Acute Lymphoblastic Leukemia. Glycobiology, 22 (1). pp. 70-83.
 
Relation http://dx.doi.org/10.1093/glycob/cwr106
http://www.eprints.iicb.res.in/1565/