ARTICLES Treatment of Philadelphia1 Leukemia in Severe Combined Immunodeficient Mice by Combination of Cyclophosphamide and bcr/abl

Background: Philadelphia1 cells are human chronic myelog-enous leukemia (CML) cells that contain the BCR/ABL on-cogene (a fusion of the BCR and ABL genes). Selective eradi-cation of these cells in vitro can be achieved by combined treatment with antisense phosphorothioate oligodeoxy-nucleotides ([S]ODNs) specifically targeted to this oncogene (bcr/abl [S]ODNs) and a suboptimal (for use as a single agent) dose of mafosfamide (the in vitro active form of cy-clophosphamide). Purpose: We evaluated the ability of bcr/ abl antisense [S]ODNs, alone or subsequent to treatment with a single injection of cyclophosphamide, to suppress the leukemic process induced in severe combined immunodefi-cient (SCID) mice by Philadelphia1 cells (i.e., primary CML-blast crisis [CML-BC] cells). In addition, we studied poten-tial mechanisms that might explain the efficacy of the bcr/ab