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Treating philadelphia ¹ Leukemia

Philadelphia ¹ cells are human chronic myelogenous leukemia cells containing the fused BCR/ABL oncogene. Skorski et al. (p. 124) report that philadelphia1 leukemia in SCID (severe combined immunodeficient) mice can be effectively treated by low-dose cyclophosphamide (to reduce toxicity) plus antisense phosphorothioate oligodeoxynucleotides ([S]ODNs) specifically targeted against that oncogene. They suggest this treatment might also be useful in humans. The researchers gave suboptimal cyclophosphamide (25% of the dose required to eradicate leukemia, if used alone), b2/a2 antisense [S]ODNs (specific for the BCR/ABL oncogene), or b3/a2 (nonspecific) antisense [S]ODNs alone or cyclophosphamide plus b2/a2 or b3/a2 antisense to SCID mice with Philadelphia ¹ leukemia.

Mice treated with b3/a2 antisense [S]ODNs alone died of leukemia within 16 weeks after injection of philadelphia1 cells. Animals treated with cyclophosphamide, b2/a2 antisense [S]ODNs, or cyclophosphamide plus b3/a2 antisense [S]ODNs lived 20-30 weeks. Among those treated with cyclophosphamide plus b2/a2 [S]ODNs, 50% lived 36-48 weeks, and 50% lived 60 weeks or more and appeared to be cured.