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

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.