Flow-cytometric Monitoring of Disease-Associated Expression of 9-O-acetylated Sialoglycoproteins in Combination With Known CD antigens, as an index for MRD in children with acute lymphoblastic leukaemia: a two-year longitudinal follow-up study
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Flow-cytometric Monitoring of Disease-Associated Expression of 9-O-acetylated Sialoglycoproteins in Combination With Known CD
antigens, as an index for MRD in children with acute lymphoblastic
leukaemia: a two-year longitudinal follow-up study
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| Creator |
Chowdhury, Suchandra
Bandyopadhyay, Suman Mandal, Chandan Chandra, Sarmila Mandal, Chitra |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Over expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs, abbreviated as OAcSGP) has been
demonstrated as a disease-associated antigen on the lymphoblasts of childhood acute lymphoblastic leukaemia (ALL). Achatinin-H, a lectin, has selective affinity towards terminal 9-O-acetylated sialic acids-α2-6-Nacetylated galactosamine. Exploring this affinity, enhanced expression of OAcSGP was observed, at the onset of disease, followed by its decrease with chemotherapy and reappearance with relapse. In spite of treatment, patients retain the diseased cells referred to as minimal residual disease (MRD) responsible for relapse. Our aim was to select a suitable template by using the differential
expression of OAcSGP along with other known CD antigens to monitor MRD in peripheral blood (PB) and bone marrow
(BM) of Indian patients with B- or T-ALL during treatment and correlate it with the disease status. A two-year longitudinal follow-up study was done with 109 patients from the onset of the disease till the end
of chemotherapy, treated under MCP841protocol. Paired samples of PB (n = 1667) and BM (n = 999) were monitored
by flow cytometry. Three templates selected for this investigation were OAcSGP+CD10+CD19+ or OAcSGP+CD34+CD19+ for B-ALL and OAcSGP+CD7+CD3+ for T-ALL. Using each template the level of MRD detection reached 0.01% for a patient in clinical remission (CR). 81.65%
of the patients were in CR during these two years while the remaining relapsed. Failure in early clearance of lymphoblasts, as indicated by higher MRD, implied an elevated risk of relapse. Soaring MRD during the chemotherapeutic regimen predicted clinical relapse, at least a month before medical manifestation. Irrespective of B- or T-lineage ALL, the MRD in PB and BM correlated well.
A range of MRD values can be predicted for the patients in CR, irrespective of their lineage, being 0.03 ±
0.01% (PB) and 0.05 ± 0.015% (BM). These patients may not be stated as normal with respect to the presence of MRD.
Hence, MRD study beyond two-years follow-up is necessary to investigate further reduction in MRD, thereby ensuring
their disease-free survival. Therefore, we suggest use of these templates for MRD detection, during and postchemotherapy for proper patient management strategies, thereby helping in personalizing the treatment.
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| Date |
2008
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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/298/1/BMC_CANCER%2C_8(_40)%2C2008%2C[125].pdf
Chowdhury, Suchandra and Bandyopadhyay, Suman and Mandal, Chandan and Chandra, Sarmila and Mandal, Chitra (2008) Flow-cytometric Monitoring of Disease-Associated Expression of 9-O-acetylated Sialoglycoproteins in Combination With Known CD antigens, as an index for MRD in children with acute lymphoblastic leukaemia: a two-year longitudinal follow-up study. BMC Cancer, 8 (40). 01-16. |
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| Relation |
http://dx.doi.org/10.1186/1471-2407-8-40
http://www.eprints.iicb.res.in/298/ |
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