Alpha-interferon reduces in vivo phosphorylation of P210bcr/abl protein during hemin-induced erythroid differentiation of K-562 cells.

Abstract

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.

• Authors: K Shibata, J Nishimura, H Takahira, H Nawata
• Journal: Experimental hematology (Exp Hematol) Vol. 19 Issue 3 Pg. 161-5 (Mar 1991) ISSN: 0301-472X [Print] Netherlands
• PMID: 1995306 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon Type I
• Tyrosine
• Hemin
• Fusion Proteins, bcr-abl

Topics

• Blast Crisis (metabolism, pathology)
• Cell Differentiation (drug effects)
• Cell Line
• Erythrocytes (cytology, drug effects)
• Erythropoiesis (drug effects)
• Fusion Proteins, bcr-abl (metabolism)
• Genes, abl
• Hemin (pharmacology)
• Humans
• Interferon Type I (pharmacology)
• Phosphorylation (drug effects)
• Precipitin Tests
• Tyrosine (metabolism)