Inhibitory effect of the anthelmintic drug pyrvinium pamoate on T315I BCR‑ABL‑positive CML cells.
Inhibitory effect of the anthelmintic drug pyrvinium pamoate on T315I BCR‑ABL‑positive CML cells.
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DOI：
10.3892/mmr.2017.7685
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发表时间：
2017-12
影响因子：
3.4
通讯作者：
Jing Zhang;Yanli Jin;Jingxuan Pan
中科院分区：
文献类型：
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作者：
Jing Zhang;Yanli Jin;Jingxuan Pan
慢性粒细胞白血病（CML）是一种克隆性骨髓增生性疾病，其特征是染色体易位，产生BCR-ABL癌基因，编码组成性激活的酪氨酸激酶。尽管第一代和第二代BCR-ABL酪氨酸激酶抑制剂（TKI）在控制慢性期CML方面取得了进展，但对于携带T315 I BCR-ABL的CML患者和晚期CML患者，尚无安全性良好的有效药物。因此，迫切需要开发针对T315 I BCR-ABL的有效疗法。在本研究中，证明了由美国食品药品监督管理局批准的驱虫药双羟萘酸吡维铵对T315 I BCR-ABL CML细胞的生长和存活具有强效抑制作用。此外，这种药物在抑制野生型和T315 I BCR-ABL CML细胞中的Wnt/β-catenin信号传导方面同样有效。因此，应进一步研究双羟萘酸吡维铵治疗携带T315 I BCR-ABL的CML患者的临床疗效。
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by a chromosome translocation that generates the BCR‑ABL oncogene, which encodes a constitutively activated tyrosine kinase. Despite progress in controlling CML at the chronic phase by first and second generations of BCR‑ABL tyrosine kinase inhibitors (TKIs), effective drugs with good safety are not available for CML patients harboring T315I BCR‑ABL and those in advanced stages of CML. Therefore, there is an urgent requirement for the development of effective therapies against T315I BCR‑ABL. In the present study, it was demonstrated that pyrvinium pamoate, an anthelmintic drug approved by the Food and Drug Administration had potent inhibitory effects on growth and survival in CML cells with T315I BCR‑ABL. In addition, this agent was equally effective in inhibiting the Wnt/β‑catenin signaling in wild‑type and T315I BCR‑ABL CML cells. Thus, the clinical efficacy of pyrvinium pamoate in treating patients with CML bearing T315I BCR‑ABL should be further investigated.