Antibodies against 9-O-acetylated sialoglycans: a potent marker to monitor clinical status in childhood acute lymphoblastic leukemia

Abstract

Background: Although childhood acute lymphoblastic leukemia (ALL) is highly responsive to chemotherapy, reliable techniques are needed to determine treatment outcome and predict impending relapse. In ALL, the cell surface over expression of 9-O-acetylated sialoglycans (9-OAcSGs) on lymphoblasts and concomitant high antibody titers in patients' sera was reported. Objectives: The present study was aimed to evaluate whether anti-9-OAcSG titers can be harnessed to monitor the clinical outcome of ALL. Design and methods: Anti-9-OAcSGs were analyzed by ELISA in children receiving either UK ALL X (n = 69, Group I) in India or UK ALL 97 (n = 47, Group II) in UK along with age-matched normal healthy controls at different time points over a period of >2 years. An attempt was also made to investigate subclass distribution of disease-specific IgG. Moreover, 17 patients having a higher sample size were longitudinally monitored. Results: Antibody levels were raised at disease presentation, decreased with remission induction, and importantly, reappeared with clinical relapse. Sera from patients with other hematological disorders and normal controls showed negligible levels of circulating anti-9-OAcSGs. In patients of both Groups I and II, the assay showed high sensitivity (98.92% and 96.77%) and specificity (92.1% and 95.91%), respectively. IgG subclass analyses during different phases of treatment revealed that 9-OAcSG-specific IgG1 could serve as a better prognostic marker in ALL. Conclusions: This study demonstrated the potential of this disease-specific antibody as an alternate marker in diagnosis and long-term assessment of ALL patients, suggesting its application in detection and prediction of impending relapse. Therefore, the expression of anti-9-OAcSGs, irrespective of their treatment protocol, may serve as an economical yet effective index for monitoring of childhood ALL.