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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.

Chowdhury S, Bandyopadhyay S, Mandal C, Chandra S, Mandal C - BMC Cancer (2008)

Bottom Line: 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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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

ABSTRACT

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.

Conclusion: 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.

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MRD in children who relapsed after a few weeks of high MRD in PB and BM during the two-year treatment phase under MCP841 protocol. MRD of five representative patients are shown (black circle) from first week of treatment. The data at diagnosis has been given for comparison. a. Represents the MRD in PB. b. Represents the MRD in BM.
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Figure 6: MRD in children who relapsed after a few weeks of high MRD in PB and BM during the two-year treatment phase under MCP841 protocol. MRD of five representative patients are shown (black circle) from first week of treatment. The data at diagnosis has been given for comparison. a. Represents the MRD in PB. b. Represents the MRD in BM.

Mentions: The remaining 11 patients (10.09% of n = 109 patients) susceptible for relapse had MRD within the normal range initially which became higher just prior to clinical relapse (Figure 6). MRD for these children increased to more than 0.1% in PB (Figure 6a) and 0.7% in BM (Figure 6b), irrespective of B or T-lineage ALL. In accordance with the previous group (Figure 5) having susceptibility of relapse predicted by less clearance of lymphoblasts, this group also had relapse mainly during the maintenance therapy. Out of 11 patients (PB = 161 samples; BM = 81 samples), relapse could however be detected only in 10 patients (9.17%). Representative profiles of MRD of five patients in PB (Figure 6a) and in BM (Figure 6b) have been revealed. These children, prior to maintenance had a low detectable level of MRD being 0.01–0.06% in PB and 0.04–0.08% in BM. However, on or after 20 weeks of treatment each of these patients had a higher MRD in both PB and BM followed by a clinical relapse at some point during maintenance. This detection could be done at least one month before the actual clinical relapse.


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.

Chowdhury S, Bandyopadhyay S, Mandal C, Chandra S, Mandal C - BMC Cancer (2008)

MRD in children who relapsed after a few weeks of high MRD in PB and BM during the two-year treatment phase under MCP841 protocol. MRD of five representative patients are shown (black circle) from first week of treatment. The data at diagnosis has been given for comparison. a. Represents the MRD in PB. b. Represents the MRD in BM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2268943&req=5

Figure 6: MRD in children who relapsed after a few weeks of high MRD in PB and BM during the two-year treatment phase under MCP841 protocol. MRD of five representative patients are shown (black circle) from first week of treatment. The data at diagnosis has been given for comparison. a. Represents the MRD in PB. b. Represents the MRD in BM.
Mentions: The remaining 11 patients (10.09% of n = 109 patients) susceptible for relapse had MRD within the normal range initially which became higher just prior to clinical relapse (Figure 6). MRD for these children increased to more than 0.1% in PB (Figure 6a) and 0.7% in BM (Figure 6b), irrespective of B or T-lineage ALL. In accordance with the previous group (Figure 5) having susceptibility of relapse predicted by less clearance of lymphoblasts, this group also had relapse mainly during the maintenance therapy. Out of 11 patients (PB = 161 samples; BM = 81 samples), relapse could however be detected only in 10 patients (9.17%). Representative profiles of MRD of five patients in PB (Figure 6a) and in BM (Figure 6b) have been revealed. These children, prior to maintenance had a low detectable level of MRD being 0.01–0.06% in PB and 0.04–0.08% in BM. However, on or after 20 weeks of treatment each of these patients had a higher MRD in both PB and BM followed by a clinical relapse at some point during maintenance. This detection could be done at least one month before the actual clinical relapse.

Bottom Line: 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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus