title: Expression of human leucocyte antigens and co-stimulatory molecules on blasts of patients with acute myeloid leukaemia.
abstract: Recently, leukaemia-associated antigens (LAA) recognized by T lymphocytes, such as Wilm's tumour-1 (WT-1) or pathogenesis-related protein-1 (PR-1), have been identified. For immunotherapies that employ antigen peptides, either alone or pulsed on dendritic cells (DC), the expression of human leucocyte antigen (HLA) molecules on the targeted leukaemic blasts (LB) is crucial. The co-stimulatory molecules CD80 and CD86 give the secondary signal to T lymphocytes that is necessary for the lysis of leukaemia cells, and CD40 enhances the efficacy of antigen presentation. Here, the expression of HLA-ABC, HLA-A2, HLA-DR, CD40, CD80 and CD86 was flow cytometrically examined in blood samples from 24 healthy volunteers (HV), 24 patients with newly diagnosed acute myeloid leukaemia (AML) and five patients with relapsed AML. The expression of HLA-ABC, CD40, CD80 and CD86 was significantly reduced on LB in comparison with monocytes of HV. HLA-A2 and HLA-DR expression was similar on LB and on monocytes of HV. In AML patients, the expression of HLA and CD86 molecules was significantly higher on LB than on CD33/CD34-negative monocytes. CD40 and CD80 molecules were deficient on AML blasts. The preservation of HLA molecules and CD86 on LB of the majority of AML patients at the time of diagnosis and even at relapse of the disease are prerequisites for LAA-targeted immunotherapies in these patients.
authors.affiliation: Third Department of Internal Medicine, University of Ulm, Ulm, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Vollmer
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Anita
authors.initials: A
authors.lastname: Schmitt
authors.forename: Jochen
authors.initials: J
authors.lastname: Greiner
authors.forename: Peter
authors.initials: P
authors.lastname: Reinhardt
authors.forename: Mark
authors.initials: M
authors.lastname: Ringhoffer
authors.forename: Markus
authors.initials: M
authors.lastname: Wiesneth
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis*; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000032:analysis; D002460:Cell Line; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000032:analysis*; D015789:HLA-A2 Antigen / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D012008:Recurrence
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D006680:HLA Antigens; D015789:HLA-A2 Antigen; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins