We investigated the use of differentiation therapy as a method of purging bone marrow (BM) of leukemic cells in ex vivo murine BM expansion cultures (Δ-cultures). In clonal cultures and in suspension cultures a combination of the differentiation-inducing agents granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, and all-trans-retinoic acid (ATRA) was found to be most effective in inducing the differentiation of the murine myelomonocytic leukemic cell line WEHI 3B D+ LacZ clone 2.8 (clone 2.8). Furthermore, we investigated the activity of a mutant form of IL-6, mutein, and found it to have a greater specific activity in cell proliferation assays and in a clone 2.8 differentiation assay than the native form of IL-6. Coculture of clone 2.8 and BM in IL-1 and kit-ligand-stimulated Δ-cultures showed that the added stimuli, G-CSF, mutein, and ATRA, decreased the expansion of leukemie cells. Mice transplanted with G-CSF, mutein, and ATRA-purged BM had an increased survival time relative to nonpurged controls. The addition of G-CSF, mutein, and ATRA to Δ-cultures did not result in any impairment of hematopoietic stem cells when measured 5 wk after transplantation.

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Supported by USPHS Grants CA-32516, CA-20194, and CA-23766 from the National Cancer Institute; DK 42639 and HL-46546 from the NIH; and the Gar Reichman Fund of the Cancer Research Institute.

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©1992 American Association for Cancer Research.
1992
American Association for Cancer Research, Inc.