Shibata K, Nishimura J, Takahira H, Nawata H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Exp Hematol. 1991 Mar;19(3):161-5.
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.
α-干扰素（IFN-α）在慢性粒细胞白血病（CML）的治疗中具有重要作用。具有增强酪氨酸激酶活性的P210bcr/abl融合蛋白与该疾病的发病机制及进展有关。为了阐明IFN-α对CML细胞增殖的抑制机制，我们研究了IFN-α对K-562细胞中P210bcr/abl的影响。尽管IFN-α抑制细胞增殖，但单独用其处理时，P210bcr/abl的磷酸化水平并未改变。然而，当K-562细胞在高铁血红素存在的情况下用低浓度（5×10²U/ml）或高浓度（10⁴U/ml）的IFN-α处理时，P210bcr/abl蛋白活性通过体内磷酸化的减少而降低，而非通过抑制从头蛋白质合成。此外，低浓度和高浓度的IFN-α与高铁血红素诱导的红系分化以及P210bcr/abl的变化同时增加血红蛋白含量。这些结果表明，IFN-α协同高铁血红素介导红系分化，因为它降低了K-562细胞中P210bcr/abl的体内酪氨酸磷酸化。
