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Updated: Mar 11, 2026
HPLC-based Assay to Monitor Extracellular Nucleotide/Nucleoside Metabolism in Human Chronic Lymphocytic Leukemia Cells
Published on: July 20, 2016
HLA-E allelic genotype correlates with HLA-E plasma levels and predicts early progression in chronic lymphocytic
Bettina Wagner1, Fabiola da Silva Nardi1,2, Sabine Schramm1
1Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.
Background:
Human leukocyte antigen-E (HLA-E) is a nonclassical major histocompatibility complex class I molecule that recently came into sharper focus as a putative marker of advanced tumor stages and disease progression. In solid tumors, increased HLA-E expression as well as elevated soluble HLA-E (sHLA-E) plasma levels are associated with a poor prognosis; however, a role for HLA-E in hematologic malignancies remains to be established.
Methods:
The authors analyzed HLA-E alleles and sHLA-E levels in a cohort of 110 individuals with chronic lymphocytic leukemia (CLL).
Results:
In patients with CLL, levels of sHLA-E increased with advanced disease stage (P = .01) and decreased after therapy (P = .01). Longitudinal follow-up revealed that both HLA-E*01:03 alleles and high levels of sHLA-E were significantly associated with a requirement for early treatment in patients with CLL (P = .027 and P = .023, respectively). In vitro, sHLA-E inhibited degranulation and interferon-γ production by natural killer (NK) cells when cocultivated with tumor cells. Moreover, sHLA-E loaded onto microspheres induced transforming growth factor-β release by NK cells. Multivariate analysis revealed that the presence of at least 1 HLA-E*01:03 allele was an independent predictor of a requirement for early treatment.
Conclusions:
HLA-E alleles and sHLA-E levels may represent novel biomarkers for early disease progression in patients with CLL. Cancer 2017;123:814-23. © 2016 American Cancer Society.
