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ACUTE MYELOID LEUKEMIA

Acute myeloid leukemia stem cells remodel the bone marrow niche via TGF-β-activated Alcam+ bone lining cells, creating a self-sustaining environment

Leukemia volume 39, pages 1778–1782 (2025)Cite this article

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TO THE EDITOR:

Relapse after achieving complete remission remains a critical challenge in the treatment of acute myeloid leukemia (AML). One of the reasons for relapse is the presence of leukemia stem cells (LSCs) [1]. LSCs are a subset of leukemia cells that possess self-renewal capabilities like normal stem cells, and they can divide to produce more LSCs and leukemia cells [2]. Like normal hematopoietic stem cells (HSCs), LSCs reside in specialized bone marrow (BM) microenvironments, termed niches, that regulate their function through complex signaling networks [3]. These niches are classified into the vascular niche in the central BM and the endosteal niche at the bone surface. The vascular niche surrounds the BM vasculature and includes mesenchymal stromal cells (MSCs), endothelial cells, and non-myelinating Schwann cells [4]. The endosteal niche at the internal bone surface consists of bone lining cells (BLCs) [5]. BLCs can be further subdivided into Alcam+ Sca-1− cells (Alcam+ BLCs), Alcam− Sca-1+ cells (Sca-1+ BLCs), and Alcam− Sca-1− cells. Sca-1+ BLCs are considered to be MSCs, whereas Alcam+ BLCs are a heterogeneous group composed mainly of osteoblasts expressing high levels of osteoblastic markers [5]. By considering the periphery of the endosteum of the BM as the endosteal niche and the central region of the BM as the vascular niche, we performed analyses to clarify the properties and characteristics of LSCs in each niche and the relationship between LSCs and each niche. Clarifying the molecular mechanisms of niche support for LSCs should provide a new perspective for the development of leukemia treatments.

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Fig. 1: Differences between the endosteal and vascular niches in LSC maintenance.
Fig. 2: Crosstalk between LSCs and Alcam+ BLCs through TGF-β1/Tgfbr2/OPN signaling.

Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by MEXT KAKENHI (grant numbers 22K08478, 23H02935 and 23K18301) and by the Chemo Sero Therapeutic Research Institute. We appreciate the technical assistance from the Research Support Center of the Research Center for Human Disease Modeling at Kyushu University Graduate School of Medical Sciences, which is partially supported by the Mitsuaki Shiraishi Fund for Basic Medical Research, and the Medical Institute of Bioregulation, Kyushu University.

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Authors and Affiliations

  1. Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Ngan Thi Kim Nguyen, Hisayuki Yao, Kentaro Hosokawa, Yuki Esaki, Ryosuke Yuta, Shunichi Adachi & Fumio Arai

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  1. Ngan Thi Kim Nguyen
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  2. Hisayuki Yao
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  3. Kentaro Hosokawa
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Contributions

NTKN, HY, and FA designed the study.; NTKN and HY contributed to the execution of the experiments and performed data analysis/representation. KH, YE, and SA generated a leukemia mouse model and supported the experiments related to leukemia cells. RY developed the experiments related to bone lining cell isolation and culturing. FA supervised the research. NTKN, HY, and FA wrote the paper. All authors have reviewed and approved the final manuscript.

Corresponding author

Correspondence to Fumio Arai.

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The authors declare no competing interests.

Ethics approval

All methods were performed in accordance with the relevant guidelines and regulations. Animal experiments have received ethical approval from the Animal Experiment Committee of Kyushu University (Approval No. A23-107-3).

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Nguyen, N.T.K., Yao, H., Hosokawa, K. et al. Acute myeloid leukemia stem cells remodel the bone marrow niche via TGF-β-activated Alcam+ bone lining cells, creating a self-sustaining environment. Leukemia 39, 1778–1782 (2025). https://doi.org/10.1038/s41375-025-02640-4

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