TRUE gene silencing is one of the gene suppression technologies. This technology exploits the enzymatic property of the tRNA 3′ processing endoribonuclease tRNase ZL, which is that it can cleave a target RNA under the direction of a small guide RNA (sgRNA). We have been working on the development of therapeutic sgRNAs for hematological malignancies. In the course of an experiment to examine the ability of the heptamer-type sgRNA H15792 targeting the OCT4 mRNA to differentiate human amnion stem cells, we observed unexpectedly that the amnion cells exhibited a morphology resembling initialized cells. Here we investigated the effect of H15792 on human HL60 leukemia cells, and found that H15792 can upregulate the OCT4 expression and the expression of alkaline phosphatase in the cells. •TRUE gene silencing is a gene suppression technology with tRNase ZL and sgRNA.•We designed and synthesized an sgRNA targeting the OCT4 mRNA.•The sgRNA induced amnion cells to take a morphology resembling initialized cells.•The sgRNA upregulated OCT4 and alkaline phosphatase expression in HL60 cells.