NT5E gene and CD38 protein as potential prognostic biomarkers for childhood B-acute lymphoblastic leukemia

Purinergic Signal. 2022 Jun;18(2):211-222. doi: 10.1007/s11302-022-09841-x. Epub 2022 Mar 2.

Abstract

The risk stratification of B-acute lymphoblastic leukemia (B-ALL) is based on clinical and biological factors. However, B-ALL has significant biological and clinical heterogeneity and 50% of B-ALL patients do not have defined prognostic markers. In this sense, the identification of new prognostic biomarkers is necessary. Considering different cohorts of childhood B-ALL patients, gene (DPP4/CD38/ENTPD1/NT5E) and protein (CD38/CD39/CD73) expressions of ectonucleotidases were analyzed in silico and ex vivo and the association with prognosis was established. In univariate analyses, expression of NT5E was significantly associated with worse progression-free survival (PFS) in bone marrow (BM) samples. In multivariate analyses, Kaplan-Meier analysis, and log-rank test, higher NT5E expression predicted unfavorable PFS in BM samples. Considering minimal residual disease (MRD), higher levels of cellularity were associated with the high NT5E expression at day 8 of induction therapy. In addition, we observed that white blood cells (WBC) of childhood B-ALL patients had more CD38 compared to the same cell population of healthy donors (HD). In fact, MRD > 0.1% patients had higher CD38 protein expression on WBC in comparison to HD. Noteworthy, we observed higher CD38 expression on WBC than blasts in MRD > 0.1% patients. We suggest that NT5E gene and CD38 protein expression, of the ectonucleotidases family, could provide interesting prognostic biomarkers for childhood B-ALL.

Keywords: CD38 protein; Childhood B-acute lymphoblastic leukemia; Ectonucleotidases; NT5E gene; Prognostic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / genetics
  • Biomarkers
  • Flow Cytometry
  • GPI-Linked Proteins
  • Humans
  • Neoplasm, Residual / drug therapy
  • Neoplasm, Residual / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Prognosis

Substances

  • Biomarkers
  • GPI-Linked Proteins
  • 5'-Nucleotidase
  • NT5E protein, human