Expression of the chronic myelogenous leukemia-associated p210bcr/abl oncoprotein in a murine IL-3 dependent myeloid cell line.
We have studied the effect of a replication-defective murine retroviral vector expressing the chronic myelogenous leukemia associated oncoprotein p210bcr/abl in murine IL-3 dependent myeloid 32D C13(G) cells. This cell line can be induced to differentiate along either the granulocytic or monocytic lineages thus permitting an independent assessment of the effect of p210bcr/abl on growth and differentiation. Cells expressing p210bcr/abl displayed a complete non-autocrine abrogation of IL-3 dependence and an enhanced response to an activity in FBS which is not IGF-I or IGF-II. During the first few generations following infection with the bcr/abl vector, cells became larger with an increased fraction of cells in G2/M and monocyte/macrophage markers were expressed. Four cytoplasmic proteins phosphorylated in response to IL-3 in the parental cell line with apparent molecular weights of 98, 70, 62, and 52 Kd were amongst those constitutively phosphorylated in p210bcr/abl expressing cells. These results suggest that the functional substitution of IL-3 by p210bcr/abl is due to constitutive activation of proteins involved in IL-3 signal transduction. Alterations of cell differentiation, cell cycle and growth which cannot be attributed to IL-3 like effects indicate that p210bcr/abl has pleiotropic effects involving several other pathways of cellular regulation.
Laneuville
P
P
Division of Hematology and Oncology, Royal Victoria Hospital, Montreal, Quebec, Canada.
Heisterkamp
N
N
Groffen
J
J
D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D016044:Fusion Proteins, bcr-abl / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D010641:Phenotype; D010750:Phosphoproteins / Q000032:analysis; D014162:Transfection
D007377:Interleukin-3; D010750:Phosphoproteins; D016179:Granulocyte Colony-Stimulating Factor; D016044:Fusion Proteins, bcr-abl