Role of CD86 in Detection of Minimal Residual Disease in Pediatric B-cell Acute Lymphoblastic Leukemia: A Prospective Study of 40 Pediatric Patients

Dr. Riva Choudhary; Dr. Smita Singh; Dr. Rushali Saxena; Dr. Shailaja Shukla; Dr. Deonath Mahto

doi:10.23958/ijirms/vol10-i05/2075

Abstract

Objective: This study aims to evaluate to utility of CD86 in minimal residual disease (MRD) detection in paediatric B-cell Acute Lymphoblastic Leukemia (ALL) for better patient management. Materials and Methods: Clinical data and flowcytometric analysis of B-cell ALL on day 0 and day 35 for MRD was collected prospectively from paediatric haematology oncology centres in India. Results: 40 children newly diagnosed with B-cell ALL between for MRD detection were enrolled in the study. Frequency of CD73, CD86 and CD123 were 90%, 70% and 60% respectively in diagnostic sample. In MRD positive samples, maximum frequency of CD86 (85.7%) and CD73 (85.7%) were observed followed by CD123 (71.4%). CD86 showed highest post-induction stability among all Leukaemia Associated Immunophenotype (LAIP) markers on blasts. Conclusion: CD86 has a significant expression in B-cell ALL in MRD detection with excellent post induction stability. Thus, inclusion of CD86 improves the utility of flowcytometry based routine clinical practice of MRD detection.

Keywords

CD86Acute lymphoblastic leukemiaMinimal residual diseaseflowcytometry

References

Cheng YQ, Zhai XW. Clinical application of minimal residual disease detection in childhood acute leukemia. Chinese Journal of Contemporary Pediatrics. 2018;20(5):416-20.Google Scholar ↗
Coustan-Smith E, Song G, Clark C, Key L, Liu P, Mehrpooya M et al. New markers for minimal residual disease detection in acute lymphoblastic leukemia. Blood. 2011;117(23):6267-76.Google Scholar ↗
Gaipa G, Basso G, Biondi A, Campana D. Detection of minimal residual disease in pediatric acute lymphoblastic leukemia. Cytometry B Clin Cytom. 2013;84(6):359-69.Google Scholar ↗
Fuda F, Chen W. Minimal/measurable residual disease detection in acute leukemias by multiparameter flow cytometry. Curr Hematol Malig Rep. 2018;13(6):455-66.Google Scholar ↗
Panda SS, Radhakrishnan V, Ganesan P, Rajendranath R, Ganesan TS, Rajalekshmy KR, et al. Flow cytometry based MRD and its impact on survival outcome in children and young adults with ALL: A prospective study from a tertiary cancer centre in southern India. Indian J Hematol Blood Transfus. 2020;36(2):300-8.Google Scholar ↗
Tembhare PR, Ghogale S, Ghatwai N, Badrinath Y, Kunder N, Patkar NV et al. Evaluation of New Markers for Minimal Residual Disease Monitoring in B‐ Cell Precursor Acute Lymphoblastic Leukemia: CD73 and CD86 Are the Most Relevant New Markers to Increase the Efficacy of MRD Assay. Cytometry Part B. 2016;94(1):100-11.Google Scholar ↗
Suvas S, Singh V, Sahdev S, Vohra H, Agrewala JN. Distinct Role of CD80 and CD86 in the Regulation of the Activation of B Cell and B Cell Lymphoma. J Biol Chem. 2002;277(10):7766-75.Google Scholar ↗
Mansour A, Elkhodary T, Darwish A, Mabed M. Increased expression of costimulatory molecules CD86 and sCTLA-4 in patients with acute lymphoblastic leukemia. Leukemia & Lymphoma. 2014;55(9):2120-4.Google Scholar ↗
Zuckerman T, Rowe JM. Pathogenesis and prognostication in acute lymphoblastic leukemia. F1000Prime Rep. 2014;6:59.Google Scholar ↗
Das, N., Banavali, S., Bakhshi, S. et al. Protocol for ICiCLe-ALL-14 (InPOG-ALL-15-01): a prospective, risk stratified, randomised, multicentre, open label, controlled therapeutic trial for newly diagnosed childhood acute lymphoblastic leukaemia in India. Trials 23, 102 (2022).Google Scholar ↗
Hock B, Patton W, Budhia S, Mannari D, Roberts P, Mckenzie J. Human plasma contains a soluble form of CD86 which is present at elevated levels in some leukaemia patients. Leukemia. 2002;16(5):865-73.Google Scholar ↗
Sedek L, Theunissen P, Costa ESD, Sluijs-Gelling AVD, Mejstrikova E, Gaipa G et al. Differential expression of CD73, CD86 and CD304 in normal vs. leukemic B-cell precursors and their utility as stable minimal residual disease markers in childhood B-cell precursor acute lymphoblastic leukemia. J of Immunol Methods. 2018; pii: S0022- 1759(17):30126-6.Google Scholar ↗
Jain S, Mehta A, Kapoor G, Bhurani D, Jain S, Agrawal N et al. Evaluating New Markers for Minimal Residual Disease Analysis by Flow Cytometry in Precursor B Lymphoblastic Leukemia. Indian J Hematol Blood Transfus. 2018;34(1):48-53.Google Scholar ↗
Wahba MA, El-Maraghy HM, Abdel-Razik AM. CD86: A Novel Prognostic Marker in Acute Lymphoblastic Leukemia Patients. The Egyptian Journal of Hospital Medicine. 2018;71(6): 3373-7.Google Scholar ↗

[refR-1] Cheng YQ, Zhai XW. Clinical application of minimal residual disease detection in childhood acute leukemia. Chinese Journal of Contemporary Pediatrics. 2018;20(5):416-20.Google Scholar ↗

[refR-2] Coustan-Smith E, Song G, Clark C, Key L, Liu P, Mehrpooya M et al. New markers for minimal residual disease detection in acute lymphoblastic leukemia. Blood. 2011;117(23):6267-76.Google Scholar ↗

[refR-3] Gaipa G, Basso G, Biondi A, Campana D. Detection of minimal residual disease in pediatric acute lymphoblastic leukemia. Cytometry B Clin Cytom. 2013;84(6):359-69.Google Scholar ↗

[refR-4] Fuda F, Chen W. Minimal/measurable residual disease detection in acute leukemias by multiparameter flow cytometry. Curr Hematol Malig Rep. 2018;13(6):455-66.Google Scholar ↗

[refR-5] Panda SS, Radhakrishnan V, Ganesan P, Rajendranath R, Ganesan TS, Rajalekshmy KR, et al. Flow cytometry based MRD and its impact on survival outcome in children and young adults with ALL: A prospective study from a tertiary cancer centre in southern India. Indian J Hematol Blood Transfus. 2020;36(2):300-8.Google Scholar ↗

[refR-6] Tembhare PR, Ghogale S, Ghatwai N, Badrinath Y, Kunder N, Patkar NV et al. Evaluation of New Markers for Minimal Residual Disease Monitoring in B‐ Cell Precursor Acute Lymphoblastic Leukemia: CD73 and CD86 Are the Most Relevant New Markers to Increase the Efficacy of MRD Assay. Cytometry Part B. 2016;94(1):100-11.Google Scholar ↗

[refR-7] Suvas S, Singh V, Sahdev S, Vohra H, Agrewala JN. Distinct Role of CD80 and CD86 in the Regulation of the Activation of B Cell and B Cell Lymphoma. J Biol Chem. 2002;277(10):7766-75.Google Scholar ↗

[refR-8] Mansour A, Elkhodary T, Darwish A, Mabed M. Increased expression of costimulatory molecules CD86 and sCTLA-4 in patients with acute lymphoblastic leukemia. Leukemia & Lymphoma. 2014;55(9):2120-4.Google Scholar ↗

[refR-9] Zuckerman T, Rowe JM. Pathogenesis and prognostication in acute lymphoblastic leukemia. F1000Prime Rep. 2014;6:59.Google Scholar ↗

[refR-10] Das, N., Banavali, S., Bakhshi, S. et al. Protocol for ICiCLe-ALL-14 (InPOG-ALL-15-01): a prospective, risk stratified, randomised, multicentre, open label, controlled therapeutic trial for newly diagnosed childhood acute lymphoblastic leukaemia in India. Trials 23, 102 (2022).Google Scholar ↗

[refR-11] Hock B, Patton W, Budhia S, Mannari D, Roberts P, Mckenzie J. Human plasma contains a soluble form of CD86 which is present at elevated levels in some leukaemia patients. Leukemia. 2002;16(5):865-73.Google Scholar ↗

[refR-12] Sedek L, Theunissen P, Costa ESD, Sluijs-Gelling AVD, Mejstrikova E, Gaipa G et al. Differential expression of CD73, CD86 and CD304 in normal vs. leukemic B-cell precursors and their utility as stable minimal residual disease markers in childhood B-cell precursor acute lymphoblastic leukemia. J of Immunol Methods. 2018; pii: S0022- 1759(17):30126-6.Google Scholar ↗

[refR-13] Jain S, Mehta A, Kapoor G, Bhurani D, Jain S, Agrawal N et al. Evaluating New Markers for Minimal Residual Disease Analysis by Flow Cytometry in Precursor B Lymphoblastic Leukemia. Indian J Hematol Blood Transfus. 2018;34(1):48-53.Google Scholar ↗

[refR-14] Wahba MA, El-Maraghy HM, Abdel-Razik AM. CD86: A Novel Prognostic Marker in Acute Lymphoblastic Leukemia Patients. The Egyptian Journal of Hospital Medicine. 2018;71(6): 3373-7.Google Scholar ↗