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

Figure 3

Metabolic adaptation lets stem cell escape oncogene addiction and oncogenic shock. Suppression of oncogenic signalling is necessary to prevent stimuli driving commitment to clonal expansion and differentiation from antagonizing the long-term maintenance of stem cell properties in the SCN. Oncogene suppression puts under stress (black arrowheads/box) stem/progenitor cells committed to clonal expansion and differentiation, which are oncogene-addicted. Thus, in the SCN, these cells would be subjected to prevalent proapoptotic stimuli and undergo the “oncogenic shock.” On the contrary, stem cells which metabolically adapt to SCN environment become independent of oncogene signalling (lose oncogene addiction) and escape oncogenic shock (white arrowheads/box), ensuring MRD maintenance.