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Role of mature leukemic cells in the amplification of leukemic stem cells in a murine model
Author(s) -
Dührsen Ulrich,
Knieling Gabriele,
Hossfeld Dieter Kurt
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910600515
Subject(s) - stem cell , clone (java method) , biology , progenitor cell , leukemia , cell culture , population , immunology , microbiology and biotechnology , macrophage , cancer stem cell , in vitro , medicine , genetics , dna , environmental health
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 interieukin 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.