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Cluster of Differentiation 96 in Children with Acute Leukemia: A Single Center Cohort Study

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Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

Abstract

Cluster of differentiation 96 (CD96) is an important leukemic stem cells (LSCs) surface marker. We evaluated CD96 expression in children with acute leukemia (AL) and described its relation with treatment response. We conducted a prospective cohort study in Mansoura University Children's Hospital, Egypt during the period from 2014 to 2016. We studied 96 children with AL and 96 controls at clinical, laboratory and radiological levels. We assessed CD96% in LSCs using flow cytometry. AL group included 59 acute lymphoblastic leukemia (ALL) and 37 acute myeloid leukemia (AML) patients. ALL subgroup involved 44 B–ALL and 15 T–ALL patients while AML subgroup included 17 M2, 12 M4 and 8 M5 patients. CD96% was higher in AL group [57.63 (21.18–89.93)] than control [34.12 (16.15–39.51)] (P < 0.001). CD96% was higher in AML [68.25 (31.1–89.86)] than ALL [54.18 (21.18–89.93] (P < 0.001). CD96% in AML was M4 > M2 > M5 (P = 0.04) while within ALL subgroup, no significant difference was found between B–ALL and T–ALL (P = 0.807). CD96% in patients with non-complete remission was higher than those with complete remission (P = 0.004). CD96 is a reliable diagnostic marker for AL mainly AML and could be used as a prognostic marker for treatment response.

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Fig. 1

Abbreviations

AL:

Acute leukemia

ALL:

Acute lymphoblastic leukemia

AML:

Acute myeloid leukemia

BM:

Bone marrow

CD:

Cluster of differentiation

CR:

Complete remission

DAPK:

Death Associated Protein Kinase

EDTA:

Ethylenediaminetetraacetic acid

FAB:

French–American–British

FACS:

Fluorescence-activated cell sorting

LSCs:

Leukemic stem cells

MAL:

Mixed lineage acute leukemia

NCR:

Non-complete remission

NK:

Natural killer

PBS:

Phosphate-buffered saline

PCR:

Polymerase chain reaction

RBCs:

Red blood cells

SE:

Standard error

References

  1. Laranjeira ABA, Yang SX (2016) Therapeutic target discovery and drug development in cancer stem cells for leukemia and lymphoma: from bench to the clinic. Expert Opin Drug Discov 11:1071–1080

    Article  CAS  Google Scholar 

  2. Pollyea DA, Gutman JA, Gore L, Smith CA, Jordan CT (2014) Targeting acute myeloid leukemia stem cells: a review and principles for the development of clinical trials. Haematologica 99:1277–1284

    Article  CAS  Google Scholar 

  3. Yabushita T, Satake H, Maruoka H et al (2018) Expression of multiple leukemic stem cell markers is associated with poor prognosis in de novo acute myeloid leukemia. Leuk Lymphoma 59:2144–2151

    Article  CAS  Google Scholar 

  4. Wang PL, O’Farrell S, Clayberger C, Krensky AM (1992) Identification and molecular cloning of tactile. A novel human T cell activation antigen that is a member of the Ig gene superfamily. J Immunol 148:2600–2608

    CAS  PubMed  Google Scholar 

  5. Fuchs A, Cella M, Giurisato E, Shaw AS, Colonna M (2004) Cutting edge: CD96 (tactile) promotes NK cell-target cell adhesion by interacting with the poliovirus receptor (CD155). J Immunol 172:3994–3998

    Article  CAS  Google Scholar 

  6. Jiang W, Zhang S, Yan J, Guo N (2013) Expression, crystallization and crystallographic study of the 1st IgV domain of human CD96. Chin J Biotechnol 29:657–663

    CAS  Google Scholar 

  7. Meyer D, Seth S, Albrecht J et al (2009) CD96 interaction with CD155 via its first Ig-like domain is modulated by alternative splicing or mutations in distal Ig-like domains. J Biol Chem 284:2235–2244

    Article  CAS  Google Scholar 

  8. Nodehi SM, Repp R, Kellner C et al (2012) Enhanced ADCC activity of affinity maturated and Fc-engineered mini-antibodies directed against the AML stem cell antigen CD96. PLoS ONE 7:e42426

    Article  CAS  Google Scholar 

  9. Du W, Hu Y, Lu C et al (2015) Cluster of differentiation 96 as a leukemia stem cell-specific marker and a factor for prognosis evaluation in leukemia. Mol Clin Oncol 3:833–838

    Article  CAS  Google Scholar 

  10. Cheson BD, Bennett JM, Kopecky KJ et al (2003) Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol 21:4642–4649

    Article  Google Scholar 

  11. Fleming S, Ong DM, Jackson K et al (2017) Partial response after induction chemotherapy has clinical relevance in acute myeloid leukaemia. Br J Haematol 177:328–330

    Article  Google Scholar 

  12. Wang XM, Yan M, Liu Y, Hailiqiguli NE (2013) CD96 expression on leukemia stem cells in 69 children with acute leukemia. Chin J Contemp Pediatr 15:633–637

    CAS  Google Scholar 

  13. Ding Y, Gao H, Zhang Q (2017) The biomarkers of leukemia stem cells in acute myeloid leukemia. Stem Cell Investig 4:19

    Article  Google Scholar 

  14. Jiang Y, Xu P, Yao D, Chen X, Dai H (2017) CD33, CD96 and death associated protein kinase (DAPK) expression are associated with the survival rate and/or response to the chemotherapy in the patients with acute myeloid leukemia (AML). Med Sci Monit Int Med J Exp Clin Res 23:1725–1732

    CAS  Google Scholar 

  15. Wu Y, Xiao M, Zhu L et al (2011) CD96 expression on bone marrow mononuclear cells in 91 patients with acute leukemia. Zhongguo shi yan xue ye xue za zhi 19:585–588

    CAS  PubMed  Google Scholar 

  16. Staudinger M, Humpe A, Gramatzki M (2013) Strategies for purging CD96+ stem cells in vitro and in vivo: new avenues for autologous stem cell transplantation in acute myeloid leukemia. Oncoimmunology 2:e24500

    Article  Google Scholar 

  17. Hosen N, Park CY, Tatsumi N et al (2007) CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia. Proc Natl Acad Sci 104:11008–11013

    Article  CAS  Google Scholar 

  18. Hailiqiguli N, Yan M (2013) Immunophenotyping of leukemic stem cells and chromosome karyotype characteristics in Uyghur leukemia pediatric patients. Chin J Oncol 35:501–504

    Google Scholar 

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Acknowledgements

We greatly acknowledge the patients and their families for their patience and help.

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Authors and Affiliations

Authors

Contributions

Hanan Mohammad: Collection of clinical data, revising the article draft and final approval of the version to be submitted. Yahya Wahba: Idea of the research, conception and design of the study, interpretation of clinical and laboratory data, drafting the article and final approval of the version to be submitted. Mona Gouida: Analysis of the laboratory data, revising the article draft and final approval of the version to be submitted. Ali Shaltout: Analysis of clinical and laboratory data, conception of the study, drafting the article and final approval of the version to be submitted.

Corresponding author

Correspondence to Yahya Wahba.

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Authors declared that they have no conflict of interest.

Ethical Standards

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee of Faculty of Medicine, Mansoura University, Egypt (Code No: MS/804) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consents were obtained from all individual participants included in the study.

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Mohammad, H., Wahba, Y., Gouida, M. et al. Cluster of Differentiation 96 in Children with Acute Leukemia: A Single Center Cohort Study. Indian J Hematol Blood Transfus 36, 178–182 (2020). https://doi.org/10.1007/s12288-019-01145-2

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