| Abstract: |
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 (∆-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 ∆-cultures showed that the added stimuli, G-CSF, mutein, and ATRA, decreased the expansion of leukemic 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 ∆-cultures did not result in any impairment of hematopoietic stem cells when measured 5 wk after transplantation. © 1992, American Association for Cancer Research. All rights reserved. |
| Keywords: |
cancer survival; controlled study; nonhuman; animal cell; mouse; animal; mice; stem cell factor; animal experiment; cell differentiation; cancer cell culture; tumor cells, cultured; mice, inbred balb c; leukemia cell; interleukin 6; interleukin-6; cell clone; recombinant granulocyte colony stimulating factor; colony-forming units assay; granulocyte colony-stimulating factor; retinoic acid; clone cells; recombinant granulocyte macrophage colony stimulating factor; bone marrow purging; tretinoin; myelomonocytic leukemia; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; hematopoietic cell growth factors; bone marrow culture; recombinant interleukin 1beta
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