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Liposomal delivery of methylphosphonate antisense oligodeoxynucleotides in
chronic myelogenous leukemia [see comments]
AM Tari, SD Tucker, A Deisseroth and G Lopez-Berestein
Department of Clinical Investigations, University of Texas M.D. Anderson
Cancer Center, Houston 77030.
Chronic myelogenous leukemia (CML) is a hematologic malignancy
characterized by the presence of the Philadelphia (Ph) chromosome. Bcr-
abl, the fusion gene associated with the Ph chromosome, expresses a
p210bcr-abl protein that promotes a selective expansion of mature myeloid
progenitor cells. Methylphosphonate (MP) oligodeoxynucleotides
complementary to specific regions of the bcr-abl mRNA were incorporated in
liposomes. We studied the effects of liposomal MP (L-MP) on the growth
inhibition of CML-like cell lines. L-MP targeted to the breakpoint
junctions of the bcr-abl mRNA inhibited the growth of CML cells. Fifty
percent inhibition was achieved at approximately 1 mumol/L of L-MP
oligonucleotide concentrations. The inhibitory effect was selective because
growth inhibition was observed only with CML but not with control cell
lines. Moreover, CML cell growth inhibition was dependent on the sequence
of the MP oligodeoxynucleotides incorporated in the liposomes. The growth
inhibition of CML cells by L-MP resulted from selective inhibition of the
expression of the p210bcr-abl protein.
Volume 84,
Issue 2,
pp. 601-607,
07/15/1994
Copyright © 1994 by The American Society of Hematology
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