Inhibitory effect of the anthelmintic drug pyrvinium pamoate on T315I BCR‑ABL‑positive CML cells.

Abstract

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.