Alpha-interferon reduces in vivo phosphorylation of P210bcr/abl protein during hemin-induced erythroid differentiation of K-562 cells.
alpha-Interferon (IFN-alpha) is important in the management of chronic myelogenous leukemia (CML). The P210bcr/abl fusion protein, with enhanced tyrosine kinase activity, is implicated in the pathogenesis and progression of the disease. To elucidate the inhibitory mechanism of IFN-alpha on CML cell proliferation, we studied the effect of IFN-alpha on P210bcr/abl in K-562 cells. The phosphorylated level of P210bcr/abl was not altered by treatment with IFN-alpha alone despite its inhibiting cell proliferation. However, when K-562 cells were treated with either a low (5 x 10(2) U/ml) or high (10(4) U/ml) concentration of IFN-alpha in the presence of hemin, P210bcr/abl protein activity decreased through reduction of in vivo phosphorylation, but not through inhibition of de novo protein synthesis. Furthermore, hemoglobin content was increased by IFN-alpha at both low and high concentrations in tandem with hemin-induced erythroid differentiation and the change in P210bcr/abl. These results demonstrate that IFN-alpha synergises hemin-mediated erythroid differentiation as it reduces the in vivo tyrosine phosphorylation of P210bcr/abl in K-562 cells.
Shibata
K
K
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nishimura
J
J
Takahira
H
H
Nawata
H
H
D001752:Blast Crisis / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects*; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D016313:Genes, abl; D006427:Hemin / Q000494:pharmacology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D014443:Tyrosine / Q000378:metabolism
D007370:Interferon Type I; D014443:Tyrosine; D006427:Hemin; D016044:Fusion Proteins, bcr-abl