The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction
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)...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2017/4979474 |
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| author | Giulia Cheloni Martina Poteti Silvia Bono Erico Masala Nathalie M. Mazure Elisabetta Rovida Matteo Lulli Persio Dello Sbarba |
| author_facet | Giulia Cheloni Martina Poteti Silvia Bono Erico Masala Nathalie M. Mazure Elisabetta Rovida Matteo Lulli Persio Dello Sbarba |
| author_sort | Giulia Cheloni |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5502d10639374e9a842c679012e235f9 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-5502d10639374e9a842c679012e235f92025-02-03T07:26:04ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/49794744979474The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene AddictionGiulia Cheloni0Martina Poteti1Silvia Bono2Erico Masala3Nathalie M. Mazure4Elisabetta Rovida5Matteo Lulli6Persio Dello Sbarba7Department of Experimental and Clinical Biomedical Sciences, Università degli Studi di Firenze, Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, Università degli Studi di Firenze, Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, Università degli Studi di Firenze, Florence, ItalyDepartment of Experimental and Clinical Medicine, Università degli Studi di Firenze, Florence, ItalyInstitute for Research on Cancer and Ageing of Nice (IRCAN), UMR CNRS 7284-INSERM U1081, Université de Nice Sophia-Antipolis, Nice, FranceDepartment of Experimental and Clinical Biomedical Sciences, Università degli Studi di Firenze, Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, Università degli Studi di Firenze, Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, Università degli Studi di Firenze, Florence, ItalyPrevious 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.http://dx.doi.org/10.1155/2017/4979474 |
| spellingShingle | Giulia Cheloni Martina Poteti Silvia Bono Erico Masala Nathalie M. Mazure Elisabetta Rovida Matteo Lulli Persio Dello Sbarba The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction Stem Cells International |
| title | The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction |
| title_full | The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction |
| title_fullStr | The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction |
| title_full_unstemmed | The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction |
| title_short | The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction |
| title_sort | leukemic stem cell niche adaptation to hypoxia versus oncogene addiction |
| url | http://dx.doi.org/10.1155/2017/4979474 |
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