INCREASED GROWTH-INHIBITION OF HUMAN CHRONIC MYELOGENOUS LEUKEMIC-CELLS BY A COMBINATION OF C-MYB ANTISENSE OLIGONUCLEOTIDE AND 4-HYDROXYPEROXYCYCLOPHOSPHAMIDE IN-VITRO
Ak. Rao et al., INCREASED GROWTH-INHIBITION OF HUMAN CHRONIC MYELOGENOUS LEUKEMIC-CELLS BY A COMBINATION OF C-MYB ANTISENSE OLIGONUCLEOTIDE AND 4-HYDROXYPEROXYCYCLOPHOSPHAMIDE IN-VITRO, International journal of oncology, 11(2), 1997, pp. 281-287
Human chronic myelogenous leukemia (CML) is a unique malignancy in its
cellular and molecular phenotypes. High dose therapy followed by stem
cell transplantation seems to be one of the most effective treatment
modalities for CML. However, allogeneic stem cell transplantation, a c
urative treatment modality, is limited due to the availability of matc
hed siblings. On the other hand, the autologous stem cell harvests are
contaminated with leukemic cells, and therefore a significant reducti
on of leukemic cells is desired before using the harvest for transplan
tation. Therefore in the present study, effects of a combination of a
suboptimal concentration of 4-hydroxyperoxycyclophosphamide (4HC) and
an optimal concentration of c-myb antisense oligonucleotide on the gro
wth of K562 human chronic myelogenous leukemic cells in vitro were det
ermined. The combination significantly (p<0.05) inhibited the growth o
f K562 cells in vitro when compared to the effects of c-myb oligonucle
otide or 4HC alone. The c-myb oligonucleotide alone or in combination
with low dose 4HC decreased the expression of c-myb gene as determined
by RT-PCR techniques. Cellular uptake and retention of fluoresceinate
d oligonucleotide in control and treated K562 cells was studied using
plain field laser microscopy and flow cytometry. There was an increase
in cellular uptake of c-myb oligonucleotide in K562 cells as measured
by plain field laser microscopy in the presence of 4HC. The combinati
on of oligonucleotides and 4HC did not significantly decrease the numb
er of hematopoietic stem/progenitor cells from normal hematopoietic st
em cell harvests as determined by in vitro colony assays. The combinat
ion of low dose 4HC and c-myb antisense oligonucleotides can potential
ly be applied in CML patients, particularly for purging leukemic cells
present in their hematopoietic stem cell harvests.