Potential Application of Differential Glycosylation in Childhood Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is a malignant transformation of lymphoblasts representing the commonest type of cancer in pediatric population. We have earlier demonstrated the differential expression of 9-O-acetylated sialoglycoproteins (9-OAcGP) [Pal et.al.2004,] as disease-associated molecules on these lymphoblasts. These are functionally active signaling molecules [Ghosh et.al.2005] capable of inducing disease-specific anti-9-OAcGP antibodies [6–8]. Subclass switching of anti-9-OAcGP from IgG1 to IgG2, alteration in their glycosylation profile along with impairment of effector functions hint toward imbalanced homeostasis thereby circumventing host defense [Bandyopadhyay et.al 2005]. Aim of the present study was to explore the expression of 9-OAcGP during chemotherapy (MCP841 protocol) and establish it as a universal marker for minimal residual disease (MRD) detection. Along with B/T- lineage-specific CD antigens, the status of 9-OAcGP have been investigated by flow cytometry in paired-samples of bone marrow (BM, 11-times from each patient) and peripheral blood (PB, 18-times from each patient) during the treatment protocol in a longitudinal follow-up study. 89 patients were monitored throughout the study period, of which the number of B-ALL and T-ALL are n =75 and n= 14 respectively. The special templates used for MRD detection, 9-OAcGP⁺CD10⁺CD19⁺/9-OAcGP⁺CD34⁺CD19⁺/9-OAcGP⁺CD7⁺CD3⁺ increased the sensitivity to 0.01% (i.e. one cancer cell could be detected in 10,000 normal cells during clinical remission)while those with high MRD followed by relapse. The number of patients having a clinical relapse during the two years treatment were n = 2. The MRD in BM correlated well with PB both in B and T- ALL. We propose that close monitoring of patients, irrespective of lineage, even in PB, may provide an efficient and reliable index for the MRD detection, enabling more long-term management of these children.