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Stem Cells International
Volume 2017, Article ID 4979474, 8 pages
https://doi.org/10.1155/2017/4979474
Research Article

The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction

1Department of Experimental and Clinical Biomedical Sciences, Università degli Studi di Firenze, Florence, Italy
2Istituto Toscano Tumori, Florence, Italy
3Department of Medical Biotechnologies (Ph.D. Programme), Università degli Studi di Siena, Siena, Italy
4Department of Experimental and Clinical Medicine, Università degli Studi di Firenze, Florence, Italy
5Institute for Research on Cancer and Ageing of Nice (IRCAN), UMR CNRS 7284-INSERM U1081, Université de Nice Sophia-Antipolis, Nice, France

Correspondence should be addressed to Matteo Lulli; ti.ifinu@illul.oettam and Persio Dello Sbarba; ti.ifinu@oisrep

Received 16 February 2017; Accepted 5 April 2017; Published 4 June 2017

Academic Editor: Eftekhar Eftekharpour

Copyright © 2017 Giulia Cheloni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Previous studies based on low oxygen concentrations in the incubation atmosphere revealed that metabolic factors govern the maintenance of normal hematopoietic or leukemic stem cells (HSC and LSC). The physiological oxygen concentration in tissues ranges between 0.1 and 5.0%. Stem cell niches (SCN) are placed in tissue areas at the lower end of this range (“hypoxic” SCN), to which stem cells are metabolically adapted and where they are selectively hosted. The data reported here indicated that driver oncogenic proteins of several leukemias are suppressed following cell incubation at oxygen concentration compatible with SCN physiology. This suppression is likely to represent a key positive regulator of LSC survival and maintenance (self-renewal) within the SCN. On the other hand, LSC committed to differentiation, unable to stand suppression because of addiction to oncogenic signalling, would be unfit to home in SCN. The loss of oncogene addiction in SCN-adapted LSC has a consequence of crucial practical relevance: the refractoriness to inhibitors of the biological activity of oncogenic protein due to the lack of their molecular target. Thus, LSC hosted in SCN are suited to sustain the long-term maintenance of therapy-resistant minimal residual disease.