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.
BACKGROUND
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-alpha2-6-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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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 post-chemotherapy for proper patient management strategies, thereby helping in personalizing the treatment.
Chowdhury
Suchandra
S
Immunobiology Division, Indian Institute of Chemical Biology, 4, Raja S, C, Mullick Road, Kolkata 700032, Kothari Medical Centre 8/3, Alipore Road, Kolkata 700027, India. suchandra_chowdhury@rediffmail.com
Bandyopadhyay
Suman
S
Mandal
Chandan
C
Chandra
Sarmila
S
Mandal
Chitra
C
D000293:Adolescent; D015703:Antigens, CD / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D008991:Monitoring, Physiologic; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism*; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012074:Remission Induction; D012795:Sialoglycoproteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D012795:Sialoglycoproteins