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Differential expression of 9-O-acetylated sialoglycoconjugates on leukemic blasts: A potential tool for long-term monitoring of children with acute lymphoblastic leukemia

✍ Scribed by Santanu Pal; Shyamasree Ghosh; Suman Bandyopadhyay; Chhabinath Mandal; Santu Bandhyopadhyay; Dilip Kumar Bhattacharya; Chitra Mandal


Book ID
102274078
Publisher
John Wiley and Sons
Year
2004
Tongue
French
Weight
189 KB
Volume
111
Category
Article
ISSN
0020-7136

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✦ Synopsis


Abstract

Earlier studies have demonstrated overexpression of 9‐O‐acetylated sialoglycoconjugates (9‐O‐AcSGs) on lymphoblasts, concomitant with high titers of anti‐9‐O‐AcSG antibodies in childhood acute lymphoblastic leukemia (ALL). Our aim was to evaluate the correlation between expression of different 9‐O‐AcSGs during chemotherapeutic treatment. Accordingly, expression of 9‐O‐AcSGs on lymphoblasts of ALL patients (n = 70) were longitudinally monitored for 6 years (1997–2002), using Achatinin‐H, a 9‐O‐acetylated sialic acid (9‐O‐AcSA) binding lectin with preferential affinity for 9‐O‐AcSGs with terminal 9‐O‐AcSAα2→6GalNAc. Western blot analysis of patients (n = 30) showed that 3 ALL‐specific 9‐O‐AcSGs (90, 120 and 135 kDa) were induced at presentation; all these bands disappeared after treatment in patients (n = 22) who had disease‐free survival. The 90 kDa band persisted in 8 patients who subsequently relapsed with reexpression of the 120 kDa band. FACS analysis revealed that at presentation (n = 70) 90.1 ± 5.0% cells expressed 9‐O‐AcSGs, which decreased progressively with chemotherapy, remained <5% during clinical remission and reappeared in relapse (80 ± 10%, n = 18). Early clearance of 9‐O‐AcSG^+^ cells, during 4–8 weeks of treatment showed a good correlation with low risk of relapse. Sensitivity of detection of 9‐O‐AcSG^+^ cells was 0.1%. Numbers of both high‐ and low‐affinity binding sites were maximum at presentation, decreased with treatment and increased again in clinical relapse. We propose that close monitoring of 90 and 120 kDa 9‐O‐AcSGs may serve as a reliable index for long‐term management of childhood ALL and merits therapeutic consideration. © 2004 Wiley‐Liss, Inc.


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