High level of sialate-O-acetyltransferase activity in lymphoblasts of childhood acute lymphoblastic leukaemia (ALL): enzyme characterization and correlation with disease status
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
High level of sialate-O-acetyltransferase activity
in lymphoblasts of childhood acute lymphoblastic
leukaemia (ALL): enzyme characterization and correlation
with disease status
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|
| Creator |
Mandal, Chandan
Srinivasan, G. Vinayaga Chowdhury, Suchandra Chandra, Sarmila Mandal, Chhabinath Schauer, Roland Mandal, Chitra |
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| Subject |
Infectious Diseases and Immunology
Structural Biology & Bioinformatics |
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| Description |
Previous studies had established an over-expression
of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs)
on lymphoblasts of childhood acute lymphoblastic leukaemia
(ALL). Here, we report the discovery and characterization
of sialate-O-acetyltransferase enzyme in ALL-cell
lines and lymphoblasts from bone marrow of children
diagnosed with B- and T-ALL. We observed a positive
correlation between the enhanced sialate-O-acetyltransferase
activity and the enhanced expression of Neu5,9Ac2-GPs
in these lymphoblasts. Sialate-O-acetyltransferase activity
in cell lysates or microsomal fractions of lymphoblasts of
patients was always higher than that in healthy donors
reaching up to 22-fold in microsomes. Additionally, the Vmax of this enzymatic reaction with AcCoA was over
threefold higher in microsomal fractions of lymphoblasts.
The enzyme bound to the microsomal fractions showed
high activity with CMP-N-acetylneuraminic acid, ganglioside
GD3 and endogenous sialic acid as substrates. Nacetyl-
7-O-acetylneuraminic acid was the main reaction
product, as detected by radio-thin-layer chromatography
and fluorimetrically coupled radio-high-performance liquid
chromatography. CMP and coenzyme A inhibited the
microsomal enzyme. Sialate-O-acetyltransferase activity
increased at the diagnosis of leukaemia, decreased with
clinical remission and sharply increased again in relapsed
patients as determined by radiometric-assay. A newlydeveloped
non-radioactive ELISA can quickly detect
sialate-O-acetyltransferase, and thus, may become a suitable
tool for ALL-monitoring in larger scale. This is the
first report on sialate-O-acetyltransferase in ALL being one
of the few descriptions of an enzyme of this type in human.
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| Publisher |
Kluwer
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| Date |
2009
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/164/1/GLYCOCONJUGATE_JOURNAL%2C26(1)%2C_57%2D73%2C2009[130].pdf
Mandal, Chandan and Srinivasan, G. Vinayaga and Chowdhury, Suchandra and Chandra, Sarmila and Mandal, Chhabinath and Schauer, Roland and Mandal, Chitra (2009) High level of sialate-O-acetyltransferase activity in lymphoblasts of childhood acute lymphoblastic leukaemia (ALL): enzyme characterization and correlation with disease status. Glycoconjugate Journal, 26. pp. 57-73. |
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| Relation |
http://dx.doi.org/10.1007/s10719-008-9163-3
http://www.eprints.iicb.res.in/164/ |
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