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

Laabi, Y; Metcalf, D; Mifsud, S; Di Rago, L

Author(s): Laabi, Y; Metcalf, D; Mifsud, S; Di Rago, L;
Details: Publication Year 2000-10,Volume 14,Issue #10,Page 1785-1795
Journal Title: LEUKEMIA
Publication Type: Journal Article
Abstract: The cloned pro-B-lymphocyte murine leukemic cell line GB2, was established from a leukemic Max41 x E mu-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-l 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 IFN gamma, 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, FAGS-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.
Publisher: NATURE PUBLISHING GROUP
Keywords: COLONY-STIMULATING FACTOR; MOUSE HEMATOPOIETIC-CELLS; MAX-41 TRANSGENIC MICE; BONE-MARROW CELLS; PROGENITOR CELLS; G-CSF; GROWTH-FACTORS; IN-VIVO; SUPPRESSION; INVITRO
Publisher's Version: https://doi.org/10.1038/sj.leu.2401931
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Creation Date: 2000-10-01 12:00:00