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
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.