Imatinib mesylate inhibits autonomous erythropoiesis in patients with polycythemia vera in vitro.

Imatinib mesylate inhibits autonomous erythropoiesis in patients with polycythemia vera in vitro.
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甲磺酸伊马替尼在体外抑制真性红细胞增多症患者的自主红细胞生成。

DOI:
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发表时间:
2003
期刊:
影响因子:
20.3
通讯作者:
K. Geissler
K. Geissler
中科院分区:
医学1区
文献类型:
--
作者:
L. Oehler;E. Jaeger;A. Eser;C. Sillaber;H. Gisslinger;K. Geissler

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真性红细胞增多症(PV)患者红细胞的过量产生在体外通过红细胞爆发形成单位(BFU-Es)的形成反映在缺乏外源性促红细胞生成素的情况下。与其他骨髓增生性疾病不同,PV的分子机制尚不清楚,也没有特异性的染色体异常被描述。我们推测甲磺酸伊马替尼可能通过抑制自主红细胞生成来逆转病理性红细胞过度生成。在本研究中,甲磺酸伊马替尼被发现阻断或强烈抑制体外自主BFU-E的形成。此外,在半固体培养基中培养前,PV电池暴露于甲磺酸伊马替尼也显著降低了BFU-E的自主生长。甲磺酸伊马替尼对自主红细胞生成的深刻影响表明,一种尚未确定的激酶参与了PV的发病机制,并应为即将进行的临床试验提供依据。
The overproduction of red blood cells in patients with polycythemia vera (PV) is reflected in vitro by the formation of erythroid burst-forming units (BFU-Es) in the absence of exogenous erythropoietin. In contrast to other myeloproliferative disorders, the molecular mechanism of PV is unknown and no specific chromosomal abnormality has been described. We speculated that imatinib mesylate may reverse the pathological overproduction of red cells by inhibition of autonomous erythropoiesis. In the present study, imatinib mesylate was found to either block or strongly inhibit autonomous BFU-E formation in vitro in all patients tested. Moreover, autonomous BFU-E growth was also markedly reduced by exposure of PV cells to imatinib mesylate prior to cultivation in semisolid medium. The profound effect of imatinib mesylate on autonomous erythropoiesis suggests the involvement of an as yet unidentified kinase in the pathogenesis of PV and should provide the rationale for a forthcoming clinical trial.
DOI: 10.1182/blood.v99.10.3792
发表时间: 2002-05-15
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影响因子: 20.3
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Holtz, MS;Slovak, ML;Bhatia, R
通讯作者: Bhatia, R
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