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Contribution of bone microenvironment to leukemogenesis and leukemia progression

Leukemia volume 23, pages 2233–2241 (2009)Cite this article

Abstract

Tumor microenvironment has a major role in cancer progression and resistance to treatment. The bone marrow (BM) is a dynamic network of growth factors, cytokines and stromal cells, providing a permissive environment for leukemogenesis and progression. Both BM stroma and leukemic blasts promote angiogenesis, which is increased in acute lymphoblastic leukemia and acute myeloid leukemia. Growth factors like vascular endothelial growth factor (VEGF), basic fibroblast growth factor and angiopoietins are the main proangiogenic mediators in acute leukemia. Autocrine proleukemic loops have been described for VEGF and angiopoietin in hematopoietic cells. Interactions of stromal cells and extracellular matrix with leukemic blasts can also generate antiapoptotic signals that contribute to neoplastic progression and persistence of treatment-resistant minimal residual disease. High expression of CXC chemokine ligand 4 (CXCR4) by leukemic blasts and activation of the CXCR4–CXCL12 axis is involved in leukemia progression and disruption of normal hematopoiesis. Leukemia-associated bone microenvironment markers could be used as prognostic or predictive indicators of disease progression and/or treatment outcome. Studies related to bone microenvironment would likely provide a better understanding of the treatment resistance associated with leukemia therapy and design of new treatments.

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Acknowledgements

This work was primarily supported by National Institutes of Health Grants DK62987, DK55001, AA13913, DK61688 and CA125550; Champalimaud Foundation, Stop and Shop Pediatric Brain Cancer Fund and funds from the Department of Medicine for the Division of Matrix Biology at Beth Israel Deaconess Medical Center. FA was supported by Grant BAE-90058 from the Health Research Fund, Ministry of Health, Spain; and by Health Service from Comunidad Autonoma of Murcia, Spain.

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  1. Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    F Ayala, R Dewar & R Kalluri

  2. Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    R Dewar

  3. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    M Kieran

  4. Department of Biological Chemistry and Molecular Pharmacology, Boston and Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Cambridge, MA, USA

    R Kalluri

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Ayala, F., Dewar, R., Kieran, M. et al. Contribution of bone microenvironment to leukemogenesis and leukemia progression. Leukemia 23, 2233–2241 (2009). https://doi.org/10.1038/leu.2009.175

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