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AML1-ETO expression is critical to for t(8 21) AML leukemogenesis and maintenance. Post-transcriptional regulation of gene expression is often mediated through transcript 3'-untranslated regions (UTR). AML1-ETO uses the 3’UTR of the ETO gene, which is not normally expressed in hematopoietic cells. Therefore, the mechanisms regulating AML1-ETO via the 3’UTR are attractive therapeutic targets. In this study, we examine the regulation of AML1-ETO via the 3’UTR. We demonstrate that AML1-ETO primarily uses a 3.7kb isoform of the ETO 3’UTR in both t(8 21) patients and cell lines. Using a luciferase assay approach, we identify an AML1-ETO 3’UTR fragment between 2.8 and 3.4kb which is negatively regulated, increases expression upon inhibition of microRNA biogenesis, and contains a putative let-7 microRNA target site. We show that let-7b directly represses AML1-ETO through this site. An analysis of The Cancer Genome Atlas AML dataset shows that let-7b and let-7 family miRNA expression is significantly lower in t(8 21) AML than other AMLs. Finally, we demonstrate that let-7b-5p inhibits the proliferation of t(8 21) AML cell lines, rescues expression of AML1-ETO target genes, and promotes differentiation. Our findings establish AML1-ETO as a let-7b target gene and suggest that let-7 based therapeutics may be applied to t(8 21) AML. Overall design: RNA-sequencing of CD34+ healthy HSPC controls and CD34+ bead-enriched AML blasts from AML patient samples. For analysis, five healthy HSPCs were sequenced and compared to eight AML patient samples, subdivided into four t(8 21) and four non-t(8 21) AML patients."],"tag":["xref:PubMed:34482400"],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"Acute myeloid leukemia (AML) patient blasts and healthy hematopoietic stem and progenitor cell (HSPC) RNA-sequencing Data","description":"Acute myeloid leukemia (AML) patient blasts and healthy hematopoietic stem and progenitor cell (HSPC) RNA-sequencing Data","dates":{"last_updated":"2025-09-24","first_public":"2022-01-01"},"accession":"PRJNA627716","cross_references":{"GEO":["GSE149237"],"taxon":["9606"],"PubMed":["34482400"]}}