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Effects of BCL-2 antisense oligodeoxynucleotides on in vitro proliferation
and survival of normal marrow progenitors and leukemic cells
L Campos, O Sabido, JP Rouault and D Guyotat
Centre de Transfusion Sanguine, Lyon, France.
Previous studies have shown that the BCL-2 protooncogene encodes a
mitochondrial protein that promotes cell survival by blocking programmed
cell death. Bcl-2 protein has been detected in normal immature myeloid
cells and in acute myeloid leukemia (AML) cells. To assess its functional
role in normal and leukemic hematopoiesis, we performed serum-free cultures
of CD34+ normal marrow cells, of bcl-2- positive myeloid lines, and of AML
cells in the presence of bcl-2 sense, nonsense, and antisense
phosphorothioate oligodeoxynucleotides. In all antisense-treated cultures,
we observed (1) an inhibition of bcl- 2 protein expression by day 4 to 6 of
culture; (2) a decrease in cell survival duration; and (3) a decrease in
the number of clonogenic cells present in the culture. Moreover, exposure
to chemotherapeutic drugs resulted in more effective killing of AML cells
in the presence of antisense oligomers. We conclude that bcl-2 protein is
necessary for the survival of myeloid cells in culture, and that it may be
implicated in the resistance of AML cells to chemotherapy.
Volume 84,
Issue 2,
pp. 595-600,
07/15/1994
Copyright © 1994 by The American Society of Hematology
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