A COMPARISON OF THE EFFECT OF BCR ABL BREAKPOINT SPECIFIC PHOSPHOTHIORATE OLIGODEOXYNUCLEOTIDES ON COLONY FORMATION BY BCR/ABL POSITIVE ANDNEGATIVE, CD34 ENRICHED MONONUCLEAR CELL-POPULATIONS/

In chronic myeloid leukaemia, the expression by clonal cells, of a leu kaemia specific bcr/abl chimeric mRNA, makes the condition suitable fo r the application of ''antisense'' strategies. Furthermore, the origin of the condition in a pluripotential progenitor allows enrichment of leukaemic clonogenic cells by selection for CD34 expression, together with a useful reduction in contaminating accessory cells. In a methylc ellulose clonogenic assay system we incubated bcr/abl expressing (n = 9) and bcr/abl negative (n = 6), CD34 enriched progenitors with phosph othiorate oligodeoxynucleotides (PS oligomers), antisense and sense to the b3a2 and b2a2 chimeric bcr/abl junctional sequences. AII samples were cloned in the presence of both antisense, and sense PS oligomers to provide appropriate controls. For bcr/abl positive progenitors, the mean number of colonies formed was reduced by 21 (39%) (P<0.05) in th e presence of the specific antisense oligomer, 11 (20%) (P<0.05) with the antisense oligomer directed to the alternative junctional breakpoi nt, and colony formation was not significantly altered by either sense PS oligomer. Colony formation by bcr/abl negative progenitors was not reproducibly reduced by any of the PS oligomers. These results confir m that PS oligomers can have a sequence dependent inhibitory effect on a CD34 enriched progenitor population from patients with chronic myel oid leukaemia. Copyright (C) 1996 Elsevier Science Ltd.