OLIGONUCLEOTIDE UPTAKE IN HUMAN HEMATOPOIETIC-CELLS IS INCREASED IN LEUKEMIA AND IS RELATED TO CELLULAR ACTIVATION

The use of antisense oligonucleotides as tools for modulating gene exp ression represents a novel strategy for designing drugs to treat a var iety of diseases. Several factors, including cellular uptake and inter nalization of the oligonucleotides, are important parameters in determ ining the effectiveness of antisense agents such as therapeutic drugs, We have studied oligonucleotides uptake in normal and leukemic human hematopoietic cells, such as peripheral blood, bone marrow (BM), and H L-60 cell line; and have found that, in normal human blood and BM, mye loid cells and B cells preferably took up more oligonucleotides than T cells. There was no marked difference in oligonucleotide uptake betwe en CD4(+) helper T cells and CD8(+) cytolytic T cells. Leukemic cells had greater oligonucleotide uptake than their normal counterparts. Fur thermore, oligonucleotide uptake was closely related to cell activatio n status and can be modulated by growth factors or inhibitors. These s tudies provide a basis for using oligonucleotides as therapeutic drugs both in vitro and in vivo.