Cytokine-driven differentiation of blasts from patients with acute myelogenous and lymphoblastic leukemia into dendritic cells

Citation
T. Kohler et al., Cytokine-driven differentiation of blasts from patients with acute myelogenous and lymphoblastic leukemia into dendritic cells, STEM CELLS, 18(2), 2000, pp. 139-147
Citations number
27
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
STEM CELLS
ISSN journal
10665099 → ACNP
Volume
18
Issue
2
Year of publication
2000
Pages
139 - 147
Database
ISI
SICI code
1066-5099(2000)18:2<139:CDOBFP>2.0.ZU;2-G
Abstract
We investigated the ability of both acute myelogenous leukemia (AML) and ac ute lymphoblastic leukemia (ALL) blasts to differentiate into dendritic cel ls (DC) in vitro, Cytokine-supplemented suspension cultures of leukemic blasts in 98 patients with AML and five patients with ALL (normal karyotype, n = 2; BCR/ABL, n = 3) mere performed. Mononuclear cells out of peripheral blood or bone marro w containing between 60% and 90% leukemic blasts were cultured for eight da ys using different growth factor combinations. The highest yield of CD1a(+)/CD14(-) cells could be obtained with stem cell factor, transforming growth factor-beta, tumor necrosis factor-alpha, GM-C SF, and FLT-3-ligand. In the AML samples the median content of CD1a(+)/CD14 (-) cells after eight days of culture was 3.5% (r = 0%-82%). In five inform ed patients CD1a(+)/CD14(-) cells were sorted by fluorescence-activated cel l sorting or immunomagnetic separation. Cytogenetic and polymerase chain re action analyses showed known primary chromosomal aberrations (monosomy 7 an d inversion 16 in the sorted fractions, respectively, Dendritic cells CDC) could be generated out of leukemic blasts in 68% of AML patients. Leukemic DC showed no phagocytosis of latex bends, but stimulated allogeneic naive c ord blood-derived T cells more efficiently than did uncultured blasts. Tn A LL patients the median percentage of CD1a(+)/CD14(-) cells was 1.2% (r = 0. 7%3.8%) after culture. The sorted CD1(+)/CD14(-) fractions were BCR/ABL-neg ative when analyzed with fluorescence in situ hybridization, indicating the ir nonleukemic origin. Leukemic DC can be generated out of leukemic progenitors in patients with A ML, These cells might become relevant for autologous and allogeneic immunot herapy in selected patients. BCR/ABL-positive lymphoblasts could not be tra nsformed into cells with an early dendritic phenotype with the cytokines us ed in our experiments.