title: Expression of CD86 in acute myelogenous leukemia is a marker of dendritic/monocytic lineage.
abstract: OBJECTIVE
  The aim of this study was to determine whether expression of the CD86 costimulatory molecule in acute myeloid leukemia (AML) can identify blast cells committed to the monocytic/dendritic lineage.
  
  
  METHODS
  One hundred ten consecutive AML patients observed at diagnosis were studied by flow cytometry. In selected experiments, in vitro cultures with CD34(+)CD86(+) or CD34(-)CD86(+) blasts were performed in the presence of granulocyte-macrophage colony-stimulating actor (GM-CSF) with or without tumor necrosis factor-alpha (TNF-alpha) or GM-CSF + interleukin-4 (IL-4), respectively, to induce a dendritic differentiation, documented by morphologic and immunophenotypic assays. T-cell alloreactivity to CD86(+) AML cells and leukemic dendritic cells (AML-DC) was tested in mixed leukocyte cultures and anti-leukemic cytotoxic assays.
  
  
  RESULTS
  CD86 was expressed in 54% AML, whereas CD80 and CD1a were only occasionally positive. CD86(+) AML samples included M5 and M4, but also 47% M0-M1 FAB types, and were more frequently CD14(+) (p < 0.00001) and CD34(-) (p = 0.00005) than CD86(-)AML. Six different patterns of CD86(+) AML were identified, according to CD34 or CD14 total or partial coexpression. Four samples enriched in CD34(+)CD86(+) AML cells differentiated into AML-DC CD86(+), CD80(+), CD40(+), CD11c(+), HLA-DR(++), CD14(+/-) that also were CD1a(+) or CD83(+), after 6 days of in vitro culture with GM-CSF +/- TNF-alpha. CD34(-)CD86(+) AML cells differentiated into AML-DC after 3 to 5 days (n = 5 experiments), and trisomy 8 was found in two AML and AML-DC samples by fluorescence in situ hybridization analysis. Finally, AML-DC induced more potent allo-T-cell proliferation, cytokine release, and anti-leukemic cytotoxicity than CD86(+) blasts.
  
  
  CONCLUSIONS
  In AML, CD86 is a marker of monocytic/dendritic lineage. Because CD86(+) blasts may differentiate into DC rapidly, CD86(+)AML patients could be optimal candidates for immunotherapy studies, both in autologous and allogeneic settings.
authors.affiliation: Institute of Hematology and Medical Oncology Seràgnoli, University of Bologna, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Re
authors.forename: Mario
authors.initials: M
authors.lastname: Arpinati
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Testoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Ricci
authors.forename: Carolina
authors.initials: C
authors.lastname: Terragna
authors.forename: Paola
authors.initials: P
authors.lastname: Preda
authors.forename: Deborah
authors.initials: D
authors.lastname: Ruggeri
authors.forename: Barbara
authors.initials: B
authors.lastname: Senese
authors.forename: Gabriella
authors.initials: G
authors.lastname: Chirumbolo
authors.forename: Valeria
authors.initials: V
authors.lastname: Martelli
authors.forename: Benedetta
authors.initials: B
authors.lastname: Urbini
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Sante
authors.initials: S
authors.lastname: Tura
authors.forename: Damiano
authors.initials: D
authors.lastname: Rondelli
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D051940:B7-2 Antigen; D014408:Biomarkers, Tumor; D019070:Cell Lineage / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D009000:Monocytes / Q000276:immunology / Q000473:pathology*
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D014408:Biomarkers, Tumor; C497964:CD86 protein, human; D008562:Membrane Glycoproteins