A 24-mer (antisense) phosphorothioate oligonucleotide (ODN) corresponding to the codons 2-9 of the
c-myb gene was evaluated for its effects on the growth of a
human Burkitt lymphoma cell line (Raji) in vitro. Raji cells
incubated with different concentrations of c-myb antisense
ODN (5-15 M-g/ml) for 24-72 h showed a significant dosedependent decrease in growth. The same concentrations of
control (sense) or scrambled c-myb phosphorothioate ODNs
did not inhibit Raji cell growth. The c-myb antisense ODN,
but not the control ODNs, significantly decreased c-myb
mRNA levels in treated cells as determined by RT-PCR.
Additionally, the c-myb antisense ODN induced apoptosis of
Raji cells as demonstrated by i) flow cytometry to enumerate
the A0 (apoptotic cell population) population of propidium
iodide stained cells; ii) electron microscopy to evaluate the
cell morphology; and iii) DNA fragmentation pattern. Thus,
an antisense c-myb ODN causes significant growth inhibition
of Burkitt lymphoma cells, and one mechanism of growth
inhibition is the induction of apoptosis of the lymphoma
cells. In addition, antisense c-myb ODN did not reduce CFUGM or BFU-e colony-forming ability of normal hematopoietic stem/progenitor cells. Because the inhibition is
sequence-specific and Burkitt lymphoma cell selective,
evaluation of the therapeutic effects of c-myb antisense ODN
against Burkitt lymphoma is warranted