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 2016; 00B: 000-000

Cytometry B Clin Cytom. 2018 Jan;94(1):100-111. doi: 10.1002/cyto.b.21486. Epub 2016 Oct 27.

Abstract

Background: Multiparametric flow cytometry (MFC) is a popular technique for minimal residual disease (MRD) analysis. However, its applicability is still limited to 90% of B-cell precursor acute lymphoblastic leukemia (BCPALL) due to two major issues, i.e. a proportion of cases do not express adequate leukemia associated immunophenotype (LAIPs) with currently used markers and drug-induced antigen modulation. Hence, the incorporation of additional reliable markers is required for the further improvement of MFC-based MRD evaluation. We studied the utility of new markers in improvising MFC-based MRD detection in BCPALL.

Methods: Expression-patterns of six new markers, i.e. CD24, CD44, CD72, CD73, CD86, and CD200 were studied in leukemic-blasts from ninety childhood BCPALL patients and in hematogones from 20 uninvolved staging bone marrow (BM) and ten postinduction non-BCPALL BM samples using eight-color MFC. The utility of these new markers in the day 35 postinduction MRD evaluation was determined.

Results: Frequencies of LAIPs of CD73, CD86, CD72, CD44, CD200, and CD24 in diagnostic samples were 76.7, 56.7, 55.6, 50, 28.9, and 20%, respectively. Differential expression of all new markers was highly significant (P < 0.01) between early (CD10+ CD19+ CD34+) hematogones, late (CD10+ CD19+ CD34-) hematogones and BCPALL blasts except between early hematogones and BCPALL blasts for CD200 (P = 0.1). In MRD-positive samples, CD73 showed the maximum (83%) frequency of LAIP and CD86 showed the highest (100%) stability of aberrant expression. Inclusion of CD73 and CD86 increased the applicability of MFC-MRD assay to 98.9% MRD samples.

Conclusion: CD73 and CD86 are the most relevant markers to incorporate in the routine MRD evaluation of BCPALL. © 2016 International Clinical Cytometry Society.

Keywords: BCPALL; CD73; CD86; MRD; flow cytometry.

MeSH terms

  • 5'-Nucleotidase / metabolism*
  • Adolescent
  • Adult
  • B-Lymphocytes / metabolism
  • B7-2 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Bone Marrow / metabolism
  • Child
  • Child, Preschool
  • Female
  • Flow Cytometry / methods
  • GPI-Linked Proteins / metabolism
  • Humans
  • Immunophenotyping / methods
  • Infant
  • Male
  • Neoplasm, Residual / metabolism*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Young Adult

Substances

  • B7-2 Antigen
  • Biomarkers, Tumor
  • CD86 protein, human
  • GPI-Linked Proteins
  • 5'-Nucleotidase
  • NT5E protein, human