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Tissue “Hypoxia” and the Maintenance of Leukemia Stem Cells

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Leukemia Stem Cells in Hematologic Malignancies

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1143))

Abstract

The relationship of the homing of normal hematopoietic stem cells (HSC) in the bone marrow to specific environmental conditions, referred to as the stem cell niche (SCN), has been intensively studied over the last three decades. These conditions include the action of a number of molecular and cellular players, as well as critical levels of nutrients, oxygen and glucose in particular, involved in energy production. These factors are likely to act also in leukemias, due to the strict analogy between the hierarchical structure of normal hematopoietic cell populations and that of leukemia cell populations. This led to propose that leukemic growth is fostered by cells endowed with stem cell properties, the leukemia stem cells (LSC), a concept readily extended to comprise the cancer stem cells (CSC) of solid tumors. Two alternative routes have been proposed for CSC generation, that is, the oncogenic staminalization (acquisition of self-renewal) of a normal progenitor cell (the “CSC in normal progenitor cell” model) and the oncogenic transformation of a normal (self-renewing) stem cell (the “CSC in normal stem cell” model). The latter mechanism, in the hematological context, makes LSC derive from HSC, suggesting that LSC share SCN homing with HSC. This chapter is focused on the availability of oxygen and glucose in the regulation of LSC maintenance within the SCN. In this respect, the most critical aspect in view of the outcome of therapy is the long-term maintenance of the LSC subset capable to sustain minimal residual disease and the related risk of relapse of disease.

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Authors and Affiliations

  1. Department of Experimental and Clinical Biomedical Sciences, Università degli Studi di Firenze, Florence, Italy

    Persio Dello Sbarba & Giulia Cheloni

  2. Cancer Research Institute, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Giulia Cheloni

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  1. Persio Dello Sbarba
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Correspondence to Persio Dello Sbarba .

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Editors and Affiliations

  1. Medical Research Institute, Wuhan University, Wuhan, Hubei, China

    Haojian Zhang

  2. Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

    Shaoguang Li

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Dello Sbarba, P., Cheloni, G. (2019). Tissue “Hypoxia” and the Maintenance of Leukemia Stem Cells. In: Zhang, H., Li, S. (eds) Leukemia Stem Cells in Hematologic Malignancies. Advances in Experimental Medicine and Biology, vol 1143. Springer, Singapore. https://doi.org/10.1007/978-981-13-7342-8_6

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