Haematologica (Mar 2024)

Small extracellular vesicles derived from acute myeloid leukemia cells promote leukemogenesis by transferring miR-221-3p

  • Mengyu Li,
  • Guohuan Sun,
  • Jinlian Zhao,
  • Shuangshuang Pu,
  • Yanling Lv,
  • Yifei Wang,
  • Yapu Li,
  • Xiangnan Zhao,
  • Yajie Wang,
  • Shangda Yang,
  • Tao Cheng,
  • Hui Cheng

DOI
https://doi.org/10.3324/haematol.2023.284145
Journal volume & issue
Vol. 999, no. 1

Abstract

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Small extracellular vesicles (sEVs) transfer cargos between cells and participate in various physiological and pathological processes through their autocrine and paracrine effects. However, the pathological mechanisms employed by sEV-encapsulated microRNAs (miRNAs) in acute myeloid leukemia (AML) are still obscure. In this study, we aimed to investigate the effects of AML cells-derived sEVs (AML-sEVs) on AML cells and delineate the underlying mechanisms. We initially used high-throughput sequencing to identify miR-221-3p as the miRNA prominently enriched in AML-sEVs. Our findings revealed that miR-221-3p promoted AML cell proliferation and leukemogenesis by accelerating cell cycle entry and inhibiting apoptosis. Furthermore, Gbp2 was confirmed as a target gene of miR-221-3p by dual luciferase reporter assays and rescue experiments. Additionally, AML-sEVs impaired the clonogenicity, particularly the erythroid differentiation ability, of hematopoietic stem and progenitor cells. Taken together, our findings reveal how sEVs-delivered miRNAs contribute to AML pathogenesis, which can be exploited as a potential therapeutic target to attenuate AML progression.