Significantly increased CD70 up regulation on TEL-AML positive B cell precursor acute lymphoblastic leukemia cells following CD40 stimulation

Klin Padiatr. 2014 Nov;226(6-7):332-7. doi: 10.1055/s-0034-1374640. Epub 2014 Jul 25.

Abstract

Background: TEL-AML the most common genetic alteration in childhood precursor B acute lymphoblastic leukemia (BCP-ALL) is associated with a favorable prognosis.

Patients and method: We studied the expression of nerve growth factor/tumor necrosis factor receptor (NGFR/TNFR)/ligand family members on 108 primary BCP-ALL samples by flow cytometry and compared both their baseline expression and CD40-induced modulation on TEL-AML positive and negative leukemia samples.

Results: Our findings demonstrate that TEL-AML positive patients exhibit a significantly higher percentage of CD40, CD27 and p75NTR positive blasts at diagnosis. This might well contribute to the improved relapse-free survival of these patients assessed in Kaplan Meier analysis as CD27 and p75NTR directly mediate apoptotic signals. Furthermore CD40 ligation enhances antigen presenting and T cell stimulatory capacity via significant up regulation of CD70 while adequate response to physiological maturation signals as indicated by concomitant down regulation of CD27 is retained in TEL-AML positive leukemia.

Conclusion: These data provide novel insights in immunological control mechanisms preserved in this leukemia subtype and suggest that not only treatment with chemicals such as HDAC inhibitors but also retained in vivo response to CD40 ligation contributes to improved immune surveillance in these patients which may add to a superior relapse-free survival observed particularly in the presence of other risk factors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • CD27 Ligand / genetics*
  • CD40 Antigens / genetics*
  • Child
  • Child, Preschool
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Female
  • Flow Cytometry
  • Humans
  • Infant
  • Male
  • Nerve Tissue Proteins / genetics
  • Oncogene Proteins, Fusion / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prognosis
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Tumor Necrosis Factor / genetics
  • Survival Rate
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Tumor Cells, Cultured / immunology
  • Tumor Cells, Cultured / pathology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics
  • Up-Regulation / genetics*

Substances

  • CD27 Ligand
  • CD40 Antigens
  • CD70 protein, human
  • Core Binding Factor Alpha 2 Subunit
  • NGFR protein, human
  • Nerve Tissue Proteins
  • Oncogene Proteins, Fusion
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • TEL-AML1 fusion protein
  • Tumor Necrosis Factor Receptor Superfamily, Member 7