Protein disulfide isomerase family is a potential therapeutic target in acute myeloid leukemia
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Acute myeloid leukemia (AML) as the second most common hematological malignancy remains currently incurable. In this study, we found the protein disulphide isomerase family (PDIs) was expressed in primary leukemia cells, with particular emphasis on ERP5 and ERP57. The compound PACMA31 demonstrated the ability to inhibit proliferation, enhance differentiation, exacerbate oxidative stress, and induce apoptosis in AML cells. RNA sequencing analysis revealed that PACMA31 impeded the proliferation of AML cells by modulating the unfolded protein response (UPR). Notably, Western blot results indicated that the antiproliferative effects of PACMA31 were mediated through the PERK/eIF2α signaling pathway. The selective inhibition of PDIs activity collectively induces apoptosis and differentiation in AML cells by activating the UPR via the PERK/eIF2α pathway. Consequently, PDIs inhibitors may represent promising candidates for the development of antitumor therapeutics against AML.
