Expression of CD86 in acute myelogenous leukemia is a marker of dendritic/monocytic lineage.
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.
Re
Francesca
F
Institute of Hematology and Medical Oncology Seràgnoli, University of Bologna, Bologna, Italy.
Arpinati
Mario
M
Testoni
Nicoletta
N
Ricci
Paolo
P
Terragna
Carolina
C
Preda
Paola
P
Ruggeri
Deborah
D
Senese
Barbara
B
Chirumbolo
Gabriella
G
Martelli
Valeria
V
Urbini
Benedetta
B
Baccarani
Michele
M
Tura
Sante
S
Rondelli
Damiano
D
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*
D015703:Antigens, CD; D051940:B7-2 Antigen; D014408:Biomarkers, Tumor; C497964:CD86 protein, human; D008562:Membrane Glycoproteins