BCR-ABL ANTISENSE OLIGODEOXYRIBONUCLEOTIDES SUPPRESS THE GROWTH OF LEUKEMIC AND NORMAL HEMATOPOIETIC-CELLS BY A SEQUENCE-SPECIFIC BUT NONANTISENSE MECHANISM

We have examined the effect of BCR/ABL junctional antisense phosphodie ster oligodeoxyribonucleotides (ODNs) on BV173 and other chronic myelo id leukemia (CML) cell lines, Various control ODNs were used to unders tand the mechanism of the observed antiproliferative effect, Not only the antisense ODNs but also several control ODNs inhibit the prolifera tion of the leukemic cell lines, All the ODNs that inhibit the cell pr oliferation share a TAT consensus sequence at their 3' end, A 1-base m ismatch within this consensus sequence abolishes the antiproliferative effect, Mismatches of several bases at any other position within the sequence of the active ODNs do not suppress the observed effect, Simil ar experiments on normal or CML CD34(+) cell fraction led to the same observations, We conclude that the antiproliferative effect of the pho sphodiester BCR/ABL antisense ODNs cannot be attributed to an antisens e mechanism but rather to a nonelucidated effect of a 3' terminal TAT sequence, This effect is not CML specific. (C) 1995 by The American So ciety of Hematology.