Vol. 130 No. 1 (2026)
Special Section: My First Manuscript

Dynamic tunnelling nanotube formation characterizes AML–Mesenchymal Stromal cell crosstalk in the Bone Marrow Microenvironment

Lavinia Pace
Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy
Bio
Silvia Masciarelli
Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy

Published 2026-09-05

Keywords

  • AML,
  • BM microenvironment,
  • tunnelling nanotubes,
  • MSC

How to Cite

Pace, L., & Masciarelli, S. (2026). Dynamic tunnelling nanotube formation characterizes AML–Mesenchymal Stromal cell crosstalk in the Bone Marrow Microenvironment. Italian Journal of Anatomy and Embryology, 130(1), 63–68. https://doi.org/10.36253/ijae-17559

Abstract

Acute myeloid leukaemia (AML) is a rapidly progressing cancer that leads to the accumulation of immature blasts in the bone marrow (BM). The BM niche, in particular mesenchymal stromal cells (MSCs), supports and protects AML cells, leading to resistance to treatment and relapses. AML blasts actively interact with mesenchymal MSCs, reshaping the niche and engaging in direct cytoplasmic exchange through tunnelling nanotubes (TNTs). Using cocultures of MOLM‑13 AML cells and MS‑5 stromal cells labelled with distinct vital dyes, we observed the rapid formation of TNTs‑like protrusions within the first hours of contact. Phalloidin staining confirmed their continuous F‑actin structure, consistent with canonical TNT morphology. Notably, TNT frequency increased following treatment, indicating that therapeutic stress enhances AML–MSC crosstalk. These findings show that AML establishes fast, dynamic physical interactions with MSCs and that TNT formation is further stimulated by treatment, highlighting TNT‑mediated crosstalk as a potential target to weaken stromal protection and improve therapeutic response.

References

  1. 1. Kayser, S. & Levis, M. J. (2018). Advances in targeted therapy for acute myeloid leukaemia. Br. J. Haematol. 180, 484–500. https://doi.org/10.1111/bjh.15032
  2. 2. Baccin, C. et al. (2020). Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization. Nat. Cell Biol. 22, 38–48. https://doi.org/10.1038/s41556-019-0439-6
  3. 3. Baryawno, N. et al. (2019). A cellular taxonomy of the bone marrow stroma in homeostasis and leukemia. Cell 177, 1915–1932.e16. https://doi.org/10.1016/j.cell.2019.04.040
  4. 4. Schepers, K., Campbell, T. B. & Passegué, E. (2015). Normal and leukemic stem cell niches: insights and therapeutic opportunities. Cell Stem Cell 16, 254–267. https://doi.org/10.1016/j.stem.2015.02.014
  5. 5. Allert, C., Müller-Tidow, C. & Blank, M. F. 2024. The relevance of the hematopoietic niche for therapy resistance in acute myeloid leukemia. Int. J. Cancer 154, 197–209. https://doi.org/10.1002/ijc.34684
  6. 6. Takahashi, S. (2020). Mutations of FLT3 receptor affect its surface glycosylation, intracellular localization, and downstream signaling. Leuk. Res. Rep. 13, 100187. https://doi.org/10.1016/j.lrr.2019.100187
  7. 7. Liccardo, F. et al. (2023). Retinoic acid and proteotoxic stress induce AML cell death overcoming stromal cell protection. J. Exp. Clin. Cancer Res. 42, 223. https://doi.org/10.1186/s13046-023-02793-z
  8. 8. Forte, D. et al. (2020). Bone marrow mesenchymal stem cells support acute myeloid leukemia bioenergetics and enhance antioxidant defense and escape from chemotherapy. Cell Metab. 32, 829–843.e9. https://doi.org/10.1016/j.cmet.2020.09.001
  9. 9. Moschoi, R. et al. (2016). Protective mitochondrial transfer from bone marrow stromal cells to acute myeloid leukemic cells during chemotherapy. Blood 128, 253–264. https://doi.org/10.1182/blood-2015-07-655860
  10. 10. Brestoff, J. R. (2025). Mitochondrial swap from cancer to immune cells thwarts anti-tumour defences. Nature 638, 42–43. https://doi.org/10.1038/d41586-025-00077-4
  11. 11. Guan, F. et al. (2024). Mitochondrial transfer in tunneling nanotubes: a new target for cancer therapy. J. Exp. Clin. Cancer Res. 43, 147. https://doi.org/10.1186/s13046-024-03069-w
  12. 12. Saito, K. et al. (2021). Exogenous mitochondrial transfer and endogenous mitochondrial fission facilitate AML resistance to OxPhos inhibition. Blood Adv. 5, 4233–4255. https://doi.org/10.1182/bloodadvances.2020003661