Flow-cytometric analysis of in vivo induction of differentiation of WEHI-3B myelomonocytic leukemia cells by recombinant granulocyte colony-stimulating factor.
An animal leukemia model was developed to investigate in vivo induction of differentiation of myeloid leukemia cells. An aneuploid cell line (C15) was isolated from mouse myelomonocytic leukemia WEHI-3B D+ cells. The C15 cells contained twice as much DNA as the parental cells but retained the morphology of myelomonocytic cells and the ability to differentiate into macrophage-like cells in response to all-trans retinoic acid (ATRA) in vitro. When the C15 cells were inoculated into the peritoneal cavity of syngeneic Balb/c mice (10(6) cells/mouse), the mice died of leukemia within 19 days. The DNA content and differentiation antigen (Mac-1) of the cells in the peritoneal cavity were determined by dual-parameter flow cytometry. On day 12 after inoculation, the C15 cells were distinguishable from normal host cells in the peritoneal cavity by their different DNA content. The administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (10 micrograms/day) to mice bearing C15 cells induced the leukemia cells to express Mac-1 antigen and to change morphologically into mature granulocytic cells. Because the C15 cells were not responsive to G-CSF in suspension culture in vitro, this result suggests that the cytokine's actions on the cells in vivo and in vitro are different. This experimental model for analyzing in vivo differentiation of leukemia cells will be useful for studying the therapeutic effects of potential differentiation-inducing agents.
Hayashi
M
M
Department of Chemotherapy, Saitama Cancer Center Research Institute, Japan.
Okabe-Kado
J
J
Hozumi
M
M
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D066298:In Vitro Techniques; D015479:Leukemia, Myelomonocytic, Acute / Q000473:pathology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D011994:Recombinant Proteins
D004273:DNA, Neoplasm; D016177:Macrophage-1 Antigen; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor