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  • Review Article
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The bone marrow stroma in hematological neoplasms—a guilty bystander

Nature Reviews Clinical Oncology volume 8, pages 456–466 (2011)Cite this article

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Abstract

In the setting of hematological neoplasms, changes in the bone marrow (BM) stroma might arise from pressure exerted by the neoplastic clone in shaping a supportive microenvironment, or from chronic perturbation of the BM homeostasis. Under such conditions, alterations in the composition of the BM stroma can be profound, and could emerge as relevant prognostic factors. In this Review, we delineate the multifaceted contribution of the BM stroma to the pathobiology of several hematological neoplasms, and discuss the impact of stromal modifications on the natural course of these diseases. Specifically, we highlight the involvement of BM stromal components in lymphoid and myeloid malignancies, and present the most relevant processes responsible for remodeling the BM stroma. The role of bystander BM stromal elements in the setting of hematological neoplasms is discussed, strengthening the rationale for treatment strategies that target the BM stroma.

Key Points

  • BM stromal changes in lymphoid malignancies are engendered by neoplastic cells to support their localization, proliferation and survival, and to suppress effective antitumor immune responses

  • Lymphoid neoplastic clones are able to manipulate the BM environment either directly, or through the co-optation of accessory cells such as macrophages and mast cells

  • Treatment strategies interfering with the axes involved in crosstalk between neoplastic cells and BM stroma may prove effective in lymphoid malignancies, when combined with therapies that target the neoplastic clones

  • Stromal alterations associated with myeloid malignancies, such as BM fibrosis, could be profound and negatively influence the clinical course of the disease and response to therapy

  • Drugs that could potentially control the proliferation of BM stromal components, such as tyrosine kinase inhibitors, proteasome inhibitors, and immunomodulatory agents are promising for the treatment of myeloid malignancies

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Figure 1: BM stroma and lymphoid infiltration.
Figure 2: Schematic representation of the interactions between lymphoid neoplastic cells and the BM stromal microenvironment.
Figure 3: Bone marrow stromal changes in myeloid malignancies.
Figure 4: Possible suppressive mechanisms of BM stromal cells.

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Authors and Affiliations

  1. Department of Human Pathology, University of Palermo, Via del Vespro 129, Palermo, 90127, Italy

    Claudio Tripodo

  2. Department of Oncology, Unit of Hematology, University of Palermo, Via del Vespro 129, Palermo, 90127, Italy

    Giovanni Franco

  3. Department of Experimental Oncology, Molecular Immunology Unit, IRCCS Istituto Nazionale Tumori, Via G. A. Amadeo, Milan, 20133, Italy

    Sabina Sangaletti & Mario P. Colombo

  4. Department of Hematology and Oncological Sciences “L. and A. Seràgnoli”, Bologna University School of Medicine, Via Massarenti 9, Bologna, 40138, Italy

    Pier P. Piccaluga & Stefano A. Pileri

  5. Hematopathology Division, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, 10065, NY, USA

    Sonam Prakash & Attilio Orazi

  6. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, Baltimore, 21231, MD, USA

    Ivan Borrello

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  1. Claudio Tripodo
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  5. Giovanni Franco
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  8. Mario P. Colombo
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  9. Stefano A. Pileri
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Contributions

C. Tripodo, S. Sangaletti, P. P. Piccaluga, S. Prakash, G. Franco, and I. Borrello researched data to include in the article. C. Tripodo, S. Sangaletti, I. Borrello, A. Orazi, M. P. Colombo, and S. A. Pileri contributed to discussion to of content for the article. All the authors contributed to the writing of the manuscript. C. Tripodo, S. Sangaletti, A. Orazi, M. P. Colombo, and S. A. Pileri reviewed/edited the manuscript before submission.

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Correspondence to Claudio Tripodo.

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Tripodo, C., Sangaletti, S., Piccaluga, P. et al. The bone marrow stroma in hematological neoplasms—a guilty bystander. Nat Rev Clin Oncol 8, 456–466 (2011). https://doi.org/10.1038/nrclinonc.2011.31

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