Colony stimulating factor-induced differentiation of murine M1 myeloid leukemia cells is permissive in early G1 phase.

Abstract

Granulocyte-colony stimulating factor (G-CSF) induces differentiation of M1 murine myeloid leukemia cells into mature granulocytes/macrophages and also causes accumulation of the cells in the G1 phase of the cell cycle. We examined, therefore, whether synchronization of M1 cells in the G1 phase could affect G-CSF-induced differentiation as quantitated by expression of Fc fragment receptors (FcR) and lysozyme activity. Cells were arrested in early G1 by density inhibition in the absence of serum and in late G1 by addition of aphidicolin. Cells synchronized in early G1, when stimulated with G-CSF, showed enhanced expression of FcR and lysozyme activity. Eighty percent of the cells expressed FcR 18 hr after addition of G-CSF while, in exponentially growing cells, this percentage was reached 72 hr after addition of G-CSF. Cells synchronized in late G1 did not show enhanced expression of differentiation markers. These results imply that with respect to G-CSF-induced differentiation, the G1 phase can be separated into an early permissive and a later nonpermissive stage.

Improved coupling between proliferation‐arrest and differentiation‐induction in ML‐1 human myeloblastic leukemia cells

“…Similarly, we have found that, as ML-1 cells differentiate, they withdraw from the cell cycle into GdGl ; thus, we anticipated that prior withdrawal into this phase might allow them to respond more rapidly to the inducing agent. This would be consistent with results from some other systems (Boyd and Metcalf, 1984;Richon et al, 1990;Sokoloski et al, 1989;Tsuda et al, 1986; but see also Yen and Albright, 1984;Yen and Chiao, 1983;Yen et al, 1988). In addition, ML-1 cell induction is enhanced by drugs that slow DNA synthesis (Craig et al, , 1985Honma et al, 1986); thus, reduced serum conditions might be expected to have a similar enhancing effect.…”

Differential expression of c‐myc and the transferrin receptor in G1 synchronized M1 myeloid leukemia cells

“…In the case of the TfR, this appears to be due to inhibition of gene transcription, but in the case of c-myc, posttranscriptional events appear to be responsible, since transcriptional activity of the c-myc gene could still be detected in a population of fully differentiated M1 cells. We have previously shown that the G1 phase of the cell cycle cannot be considered to be a homogeneous period with respect to sensitivity of M1 cells to differentiation (Tsuda et al, 1986). Synchronization in early G1 is supportive of differentiation, while synchronization in late GI is not.…”

Specific binding of murine leukemia inhibitory factor to normal and leukemic monocytic cells.

“…Both 1251I-LIF and unlabeled LIF from the same original fraction were diluted to the same final concentration and assayed in parallel for their capacity to induce the differentiation of Ml cells as described (20 Binding was carried out as described (19). Cells were resuspended in RPMI 1640 medium containing 10 rocal of cell number versus reciprocal 125I-LIF specifically bound (Fig. 1B), the maximal amount of 125I-LIF capable of binding specifically was determined from the extrapolated intercept on the ordinate (infinite cell number).…”

“…Amino acid sequencing (7) and the resultant cloning and sequencing of the cDNA encoding murine LIF (8) demonstrated it to be distinct from other molecules such as G-CSF (9)(10)(11), interferon P, interleukin 1 (IL-1), tumor necrosis factor (12), and IL-6 (D.M., unpublished observation) affecting the proliferation and differentiation of Ml leukemic cells. The latter molecules are known to have a variety of actions on normal and neoplastic cells (13)(14)(15)(16)(17).…”