GROWTH-INHIBITION OF CHRONIC MYELOGENOUS LEUKEMIA-CELLS BY ODN-1, AN APTAMERIC INHIBITOR OF P210(BCR-ABL) TYROSINE KINASE-ACTIVITY

p210(bcr-abl)-Related tyrosine kinase activity has been shown to cause chronic myelogenous leukemia (CML), a disease of bone marrow stem cel ls, Having previously demonstrated that the aptameric oligonucleotide, ODN-1, could inhibit p210(bcr-abl) kinase activity, the current study sought to determine if ODN-1 could selectively inhibit the growth of CML cells relative to that of normal bone marrow. ODN-1, when introduc ed by electroporation into peripheral blood mononuclear cells (PBMC) f rom patients with CML, decreased the number of committed progenitors ( CML CFU-GM) by an average of 67% +/- 19% (mean +/- SEM, range 28-98%), Treatment of CML PBMC with ODN-1 was also shown to decrease the numbe r of more primitive cobblestone area-forming cells (CAFC) by 35%-87%, In contrast, there was little suppressive effect by the combination of electroporation and ODN-1 on either CFU-GM or CAFC numbers from norma l donor bone marrow. These studies suggest that inhibition of p210(bcr -abl) protein-tyrosine kinase (PTK) activity by ODN-1 is associated wi th some degree of selective growth inhibition of p210(bcr-abl)-transfo rmed cells. p210(bcr-abl) kinase inhibitory agents may be useful for t he ex vivo purging of bone marrow or peripheral blood progenitor/stem cells in the setting of autologous transplantation for CML.