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

Abstract

The cloned pro-B-lymphocyte murine leukemic cell line GB2, was established from a leukemic Max41 x E -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 IFN␥, 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 granulocytemacrophage 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. Leukemia (2000) 14, 1785-1795.

Reversible growth factor dependency and autonomy during murine myelomonocytic leukemia induced by oncogenes

“…In view of the maturation-inducing effects of some cytokines on colonies formed by M1, WEHI3B, or GB2 leukemic cells (12)(13)(14), the possible suppressive effects of IL-6, leukemia inhibitory factor (LIF), or G-CSF alone, or in combination, were examined in sequential recultures of MLL-ENL or MLL-AF9 leukemic colonies. However, no evidence was obtained that the three cytokines tested were able to induce morphological changes in the leukemic colony cells or to reduce their clonogenicity.…”

The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology

“…Organoid or enteroid cultures that are differentiated have lost their proliferation ability and stemness but may not be fully mature. Maturation denotes cells that are committed to a specific lineage and are somewhere in development to the final mature cell (43, 44). For example, to form a goblet cell, stem cells in the in vivo intestine will differentiate to precursor cells that begin to show signs of mucous granules but do not yet express the full protein signature of a functional goblet cell (45).…”

Hematopoietic cytokines

“…67 With certain leukemias, cytokines had an even more dramatic action in inducing the leukemic cells to behave as appropriate normal progenitor cells. 68 Definitive evidence that inserted receptors could induce differentiation commitment was obtained by inserting IL-2R␤ receptors into common lymphoid progenitor cells, which up-regulated GM-CSF receptors, allowing stimulation of granulocyte and macrophage formation by GM-CSF. 69 Maturation initiation was reported in unstimulated factor-dependent continuous cell lines, where viability was maintained by overexpression of bcl2.…”