Y-box binding protein 1 in small extracellular vesicles reduces mesenchymal stem cell differentiation to osteoblasts-implications for acute myeloid leukaemia

J Extracell Vesicles. 2024 Mar;13(3):e12417. doi: 10.1002/jev2.12417.


Small extracellular vesicles (sEVs) released by acute myeloid leukaemia (AML) cells have been reported to influence the trilineage differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, it remains elusive which biological cargo from AML-sEVs is responsible for this effect. In this study, sEVs were isolated from cell-conditioned media and blood plasma using size-exclusion chromatography and ultrafiltration and characterized according to MISEV2018 guidelines. Our results demonstrated that AML-sEVs increased the proliferation of BM-MSCs. Conversely, key proteins that are important for normal haematopoiesis were downregulated in BM-MSCs. Additionally, we revealed that AML-sEVs significantly reduced the differentiation of BM-MSCs to osteoblasts without affecting adipogenic or chondrogenic differentiation. Next, LC-MS/MS proteomics elucidated that various proteins, including Y-box-binding protein 1 (YBX1), were upregulated in both AML-sEVs and BM-MSCs treated with AML-sEVs. Clinically relevant, we found that YBX1 is considerably upregulated in most paediatric AML patient-derived sEVs compared to healthy controls. Interestingly, sEVs isolated after the downregulation of YBX1 in AML cells remarkably rescued the osteoblastic differentiation of BM-MSCs. Altogether, our data demonstrate for the first time that YBX1 containing AML-sEVs is one of the key players that disrupt the normal function of bone marrow microenvironment by reducing the osteogenic differentiation of BM-MSCs.

Keywords: Y-box binding protein 1; acute myeloid leukaemia; bone marrow microenvironment; mesenchymal stem cells; osteoblasts; small extracellular vesicles.

MeSH terms

  • Child
  • Chromatography, Liquid
  • Extracellular Vesicles* / metabolism
  • Humans
  • Leukemia, Myeloid, Acute*
  • Mesenchymal Stem Cells* / metabolism
  • Osteoblasts
  • Osteogenesis
  • Tandem Mass Spectrometry
  • Tumor Microenvironment
  • Y-Box-Binding Protein 1 / metabolism


  • Y-Box-Binding Protein 1
  • YBX1 protein, human