RAB27B-regulated exosomes mediate LSC maintenance via resistance to senescence and crosstalk with the microenvironment

Transforming the Niche: The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression

“…Most interestingly, LSCs seem to use exosome export machinery to diminish intracellular levels of tumour suppressor elements as a means to escape control. Consistently, Chen et al showed that LSCs overexpress RAB27B, a gene regulating exosome secretion, which is associated with poor prognosis in AML patients [92]. Importantly, the authors demonstrate that increased RAB27B in LSCs prevents their senescence and maintains their stemness both in vitro and in vivo.…”

“…Importantly, the authors demonstrate that increased RAB27B in LSCs prevents their senescence and maintains their stemness both in vitro and in vivo. Mechanistically, LSCs seem to selectively promote the loading and release of exosomes rich in senescence-inducing proteins and other elements, such as miR-34c-5p, bypassing p53/p21/cyclin-dependent or p53independent tumour suppressor checkpoints [56,92]. Interestingly, AML cell-derived EVs carrying miR-1246 also seem to target both LSCs and other leukaemic blasts.…”

“…Indeed, Abdul-Aziz et al [128] have described that AML-generated NOX2-derived superoxide can also trigger a pro-leukaemic p16INK4a-dependent senescence in BMMSCs. Interestingly, LSCs also seem to shed large amounts of exosomes rich in senescence-inducing proteins to further reinforce BMMSC senescence, luring them to selectively produce exosomes rich in stemness-promoting proteins to their own advantage [92]. Most importantly, targeting senescent BMMSCs directly inhibited AML blast proliferation and enhanced the survival of leukaemia-bearing mice.…”

Extracellular vesicles in non-small cell lung cancer stemness and clinical applications

“…These data suggest that RAB27B may be involved in regulating the cargo content of NSCLC CSC-derived EVs. Similarly, RAB27B is upregulated in CD34 + acute myeloid leukemia (AML) CSCs and to plays a role in the stemness of these cells (91). Mechanistically, RAB27B directly interacts with senescence-associated proteins in AML CSCs to promote their selective loading into secreted exosomes.…”

“…Mechanistically, RAB27B directly interacts with senescence-associated proteins in AML CSCs to promote their selective loading into secreted exosomes. In addition, AML CSCderived exosomes enriched with senescent-associated proteins remodeled the CSC niche to induce senescence of mesenchymal stem cells (MSCs) in a RAB27B-dependent manner (91). These senescent MSCs in turn secreted exosomes enriched with stemnesspromoting proteins to maintain stemness in AML cells.…”