The activity of NF-kB/Rel nuclear factors is known to inhibit
apoptosis in various cell types. We investigated whether the
subtraction of NF-kB/Rel activity influenced the response of
11 AML (M1, M2 and M4) patients’ cells to AraC. To this
end we used a phosphorothioate double-stranded decoy oligodeoxynucleotide
(ODN) carrying the NF-kB/Rel- consensus
sequence. Cell incubation with this ODN, but not its
mutated (scrambled) form used as a control, resulted in
abating the NF-kB/Rel nuclear levels in these cells, as verified
by electrophoretic mobility shift assay (EMSA) of cells’
nuclear extracts. We incubated the leukemic cells with AraC
(32 or 1 mM), in either the absence or presence of the decoy or the scrambled ODN, and analyzed cell apoptosis. The
spontaneous cell apoptosis detectable in the absence of
AraC (,25%) was not modulated by the oligonucleotide
presence in cell cultures. On the other hand, in 10 of the 11
samples tested, the decoy kB, but not the scrambled ODN
significantly (P ,0.01 in a Student’s t test) enhanced cell
apoptotic response to AraC. Such an effect was particularly
remarkable at low AraC doses (1 mM). These findings indicate
that NF-kB/Rel activity influences response to AraC in
human primary myeloblastic cells, and suggests that the
inhibition of NF-kB/Rel factors can improve the effect of
chemotherapy in AM
