Alternative polyadenylation (APA) is a post-transcriptional process that typically determines the length of mature mRNAs' 3' untranslated region (3'UTR). The global shortened 3'UTR alters mRNA stability, localization, and translation and contributes to cancer progression.1 The APA characteristics and its effects on acute myeloid leukemia (AML) remain to be comprehensively described. Here, we identified churchill domain containing 1 (CHURC1) as an up-regulated gene with a lengthened 3'UTR in CD34+ enriched AML cells compared with healthy hematopoietic stem and progenitor cells. As for APA regulation of CHURC1, we found that rs6745 and RNA binding protein TIA1 potentially contribute to the distal poly(A) site usage in cis- and trans-ways, respectively. Mechanistically, a lengthened CHURC1 3'UTR affected the apoptosis of AML cells by disrupting the expression of DICER1 by sponging miR-186–5p. The chemotherapeutic sensitivity of 8 drugs was associated with CHURC1 poly(A) site usage. Overall, our analysis indicated a previously undetected gene, CHURC1, that affected AML progression through 3'UTR length change resulting from APA. Data collection and detailed analysis methods were described in the supplementary material.