The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Leukaemogenesis induced by an activating β-catenin mutation in osteoblasts
Open accessAbstract
Cells of the osteoblast lineage affect the homing and the number of long-term repopulating haematopoietic stem cells, haematopoietic stem cell mobilization and lineage determination and B cell lymphopoiesis. Osteoblasts were recently implicated in pre-leukaemic conditions in mice. However, a single genetic change in osteoblasts that can induce leukaemogenesis has not been shown. Here we show that an activating mutation of β-catenin in mouse osteoblasts alters the differentiation potential of myeloid and lymphoid progenitors leading to development of acute myeloid leukaemia with common chromosomal aberrations and cell autonomous progression. Activated β-catenin stimulates expression of the Notch ligand jagged 1 in osteoblasts. Subsequent activation of Notch signalling in haematopoietic stem cell progenitors induces the malignant changes. Genetic or pharmacological inhibition of Notch signalling ameliorates acute myeloid leukaemia and demonstrates the pathogenic role of the Notch pathway. In 38% of patients with myelodysplastic syndromes or acute myeloid leukaemia, increased β-catenin signalling and nuclear accumulation was identified in osteoblasts and these patients showed increased Notch signalling in haematopoietic cells. These findings demonstrate that genetic alterations in osteoblasts can induce acute myeloid leukaemia, identify molecular signals leading to this transformation and suggest a potential novel pharmacotherapeutic approach to acute myeloid leukaemia.
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Cites
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Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia
Raaijmakers, M. H. G. P., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., et al. (2010) · Nature · doi:10.1038/nature08851 · Cited by 1,115
Self-citationCirculating Osteoblast-Lineage Cells in Humans
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Notch activation inhibits AML growth and survival: a potential therapeutic approach
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Valkenburg, K. C., de Groot, A. E., & Pienta, K. J. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0007-1 · Cited by 1,084
Osteoimmunology: The conceptual framework unifying the immune and skeletal systems
Okamoto, K., Nakashima, T., Shinohara, M., Negishi-Koga, T., Komatsu, N., Terashima, A., Sawa, S., Nitta, T., & Takayanagi, H. (2017) · Physiological Reviews · doi:10.1152/physrev.00036.2016 · Cited by 534
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Zambetti, N. A., Ping, Z., Chen, S., Kenswil, K. J. G., Mylona, M. A., Sanders, M. A., Hoogenboezem, R. M., Bindels, E. M. J., Adisty, M. N., Van Strien, P. M. H., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.08.021 · Cited by 342
The hematopoietic stem cell niche: from embryo to adult
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Metadata
- Authors
- Kode, A., Manavalan, J. S., Mosialou, I., Bhagat, G., Rathinam, C. V., Luo, N., Khiabanian, H., Lee, A., Murty, V. V., Friedman, R., Brum, A., Park, D., Galili, N., Mukherjee, S., Teruya-Feldstein, J., Raza, A., Rabadan, R., Berman, E., & Kousteni, S.
- Venue
- Nature
- Published
- 2014-01-15
- Volume
- 506
- Issue
- 7487
- Pages
- 240-244
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2114409684
- Cited by
- 532
- References
- 7
- FWCI
- 42.65
- Type
- journal article
- Language
- en
- Open access
- green
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
