Expression of RANK-L and in part of PD-1 on blasts in patients with acute myeloid leukemia correlates with prognosis

Eur J Haematol. 2016 Dec;97(6):517-527. doi: 10.1111/ejh.12762. Epub 2016 Jun 5.

Abstract

Background: Co-stimulatory receptor (COR) and ligand (COL) expression on immune effectors are known to be relevant for immunological interactions and might be of prognostic relevance if expressed on acute myeloid leukemia (AML) blasts as reported for receptors of the tumor necrosis factor receptor family.

Aim and methods: Antigen expression profiling of COR (RANK, PD-1), COL (RANK-L, PD-1L), and HLA-ABC-antigens on blasts from 90 AML-patients at first diagnosis was performed by flow cytometry (SFI-Level characterization) and findings were correlated with clinical parameters.

Results: RANK expression was higher in immature compared to mature FAB groups (P = 0.08). As a monocytic marker, we identified HLA-ABC (P = 0.07). Prognostic analysis revealed a higher probability of overall survival in cases with lower RANK-L expression (<1.6 and ≥1.6, 15.6 vs. 12.2 months, P = 0.008, hazard ratio 0.36, P = 0.008). No significant impact of PD-1/L expression for patients'(pts) survival was seen but a correlation of PD-1 with a secondary AML (P = 0.03). Prolonged disease-free survival however correlated with higher PD-1 expression (≥1.1 vs. <1.1, 31.4 vs. 12.7 months; P = 0.03).

Conclusion: Our study revealed that RANK-L is a promising marker to forecast pts' prognosis in AML. Immune checkpoint receptor PD-1/L as well as RANK and HLA-ABC did not show an impact on pts' survival.

Keywords: Receptor activator of nuclear factor kappa-B ligand; acute myeloid leukemia; human leukocyte antigen molecule class I; prognosis; programmed death-1; programmed death-1/Ligand.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Cytogenetic Analysis
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Immunophenotyping
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality*
  • Male
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / genetics*
  • Programmed Cell Death 1 Receptor / metabolism
  • RANK Ligand / genetics*
  • RANK Ligand / metabolism
  • Recurrence
  • Young Adult

Substances

  • Biomarkers
  • Programmed Cell Death 1 Receptor
  • RANK Ligand