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Animal Models

Differentiation commitment and regulator-specific granulocyte–macrophage maturation in a novel pro-B murine leukemic cell line

Leukemia volume 14, pages 1785–1795 (2000)Cite this article

Abstract

The cloned pro-B-lymphocyte murine leukemic cell line GB2, was established from a leukemic Max41 x Eμ-myc double transgenic mouse. Its Igh alleles are rearranged and its surface markers are primarily B-lymphoid, but a small proportion of the cells also express surface Gr-1 and some cells develop the morphology of maturing granulocytes. The cell line grows continuously in suspension culture without the addition of growth factors, but expresses mRNA for M-CSF, TPO and Flt-3-ligand. When stimulated in agar cultures by GM-CSF, G-CSF, M-CSF, IL-3, SCF, IL-6, leukemia inhibitory factor (LIF), IL-5 or IFNγ, GB2 cells generated blast colonies or colonies of maturing granulocytes and macrophages. There was a striking similarity in colony types, relative colony numbers and maturation of colony cells to those formed by normal bone marrow cells in response to the same stimuli. GB2 blast colony-forming cells exhibited self-renewal as well as an ability to form granulocyte–macrophage colony-forming progeny, with evidence that a hierarchical sequence of clonogenic cells is generated in the cell line even after subcloning. Factor-specific maturation was clearly initiated by the action of the added growth factors. In contrast, FACS-sorting experiments showed that commitment to various types of colony-forming cell occurs in maintenance suspension cultures in the apparent absence of potentially relevant growth factors.

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Acknowledgements

This work was supported by the Carden Fellowship Fund of the Anti-Cancer Council of Victoria, the National Health and Medical Research Council, Canberra and the National Institutes of Health, Bethesda, Grant Nos CA-22556 and CA-43540. The authors are indebted to Drs AW Harris and JM Adams for their critical review of the manuscript.

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  1. The Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Victoria, 3050, Australia

    Y Laâbi, D Metcalf, S Mifsud & LDi Rago

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Laâbi, Y., Metcalf, D., Mifsud, S. et al. Differentiation commitment and regulator-specific granulocyte–macrophage maturation in a novel pro-B murine leukemic cell line. Leukemia 14, 1785–1795 (2000). https://doi.org/10.1038/sj.leu.2401931

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