| First Author | Dührsen U | Year | 1995 |
| Journal | Int J Cancer | Volume | 60 |
| Issue | 5 | Pages | 652-9 |
| PubMed ID | 7860140 | Mgi Jnum | J:23273 |
| Mgi Id | MGI:71039 | Doi | 10.1002/ijc.2910600515 |
| Citation | Duhrsen U, et al. (1995) Role of mature leukemic cells in the amplification of leukemic stem cells in a murine model. Int J Cancer 60(5):652-9 |
| abstractText | The recently described PGM-2 leukemia displays a hierarchical structure with bipotential stem cells, B-lymphocyte and macrophage progenitor cells, and post-mitotic end cells. Because the different cell types can easily be identified in vitro by clonal culture assays and simple staining procedures, this leukemia is a useful model for the study of the interactions between different cell compartments in a leukemic clone. Our analysis of the impact of mature leukemic macrophages on the proliferation of stem cells was facilitated by the establishment of long-term cultures producing new stem cells over prolonged periods of time. A prerequisite was the development of an adherent layer of fibroblasts and leukemic macrophages. Enumeration of adherent cells revealed a good correlation between the number of macrophages and the number of stem cells generated, and expansion of the macrophage population by treatment with interleukin 3 (IL-3) resulted in a significant improvement of the culture conditions. Leukemic macrophages were also able to induce the formation of stem-cell colonies in agar culture, suggesting a role for humoral mediators. Antibody neutralization experiments and bioassays identified IL-7 and IL-6 as factors cooperating in the stimulation of stem-cell self-renewal. Feed-back stimulation of leukemic stem cells by mature leukemic cells may also be relevant to human leukemias and have implications for differentiation therapy. |
