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

作者：Cheloni Giulia; Poteti Martina; Bono Silvia; Masala Erico; Mazure Nathalie M; Rovida Elisabetta; Lulli Matteo^*; Dello Sbarba Persio^*

来源：Stem Cells International, 2017, 2017: 4979474.

DOI：10.1155/2017/4979474

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-termmaintenance of therapy-resistantminimal residual disease.

• 出版日期2017