title: HLA-E allelic genotype correlates with HLA-E plasma levels and predicts early progression in chronic lymphocytic leukemia.
abstract: 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.
  
  
  
  The authors analyzed HLA-E alleles and sHLA-E levels in a cohort of 110 individuals with chronic lymphocytic leukemia (CLL).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Wagner
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.|Coordinaton for the Improvement of Higher Education Personnel (CAPES) Foundation, Ministry of Education of Brazil, Brasilia, Brazil.
authors.forename: Fabiola
authors.initials: F
authors.lastname: da Silva Nardi
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schramm
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kraemer
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Celik
authors.affiliation: Department of Hematology, University Hospital Essen, Essen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Horn
authors.affiliation: Department of Hematology, University Hospital Essen, Essen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dührsen
authors.affiliation: Department of Hematology, University Hospital Essen, Essen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Nückel
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Rebmann
mesh_terms: D000368:Aged; D000483:Alleles; D014408:Biomarkers, Tumor / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000235:genetics* / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000097625:HLA-E Antigens
chemical_list: D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens
keywords: chronic lymphocytic leukemia (CLL); human leukocyte antigen-E (HLA-E); immune escape; natural killer (NK) cells