Pro-inflammatory cytokines favor the emergence of ETV6-RUNX1-positive pre-leukemic cells in a model of mesenchymal niche.

ETV6-RUNX1 (E/R) fusion gene, arising in utero from translocation t(12;21)(p13:q22), is the most frequent alteration in childhood acute lymphoblastic leukemia (ALL). However, E/R is insufficient to cause overt leukemia since it generates a clinically silent pre-leukemic clone which persists in the bone marrow but fails to out-compete normal progenitors. Conversely, pre-leukemic cells show increased susceptibility to transformation following additional genetic insults. Infections/inflammation are the most accredited triggers for mutations accumulation and leukemic transformation in E/R+ pre-leukemic cells. However, precisely how E/R and inflammation interact in promoting leukemia is still poorly understood. Here we demonstrate that IL6/TNFα/ILβ pro-inflammatory cytokines cooperate with BM-MSC in promoting the emergence of E/R+ Ba/F3 over their normal counterparts by differentially affecting their proliferation and survival. Moreover, IL6/TNFα/ILβ-stimulated BM-MSC strongly attract E/R+ Ba/F3 in a CXCR2-dependent manner. Interestingly, E/R-expressing human CD34+ IL7R+ progenitors, a putative population for leukemia initiation during development, were preserved in the presence of BM-MSC and IL6/TNFα/ILβ compared to their normal counterparts. Finally, the extent of DNA damage increases within the inflamed niche in both control and E/R-expressing Ba/F3, potentially leading to transformation in the apoptosis-resistant pre-leukemic clone. Overall, our data provide new mechanistic insights into childhood ALL pathogenesis

'You don't have to be black skinned to be black': Indigenous young people's bodily practices

In contemporary Western societies, disciplinary and normalising technologies function to create a sense of moral obligation within each individual to monitor and regulate the body in terms of health, including diet and exercise. The settler/Aboriginal experience in Australia provides an example of the ways in which biopolitics has operated at a population level for all Australians and in specific ways for Indigenous bodies. This study sought to explore the perceptions of a group of urban Indigenous young people regarding their views of their bodies in the context of health and physical activity. Using the lens of biopolitics, complemented by post-colonial theory, this paper will draw attention to the ways in which historical and current discourses around Indigenous health might illustrate biopolitical technologies of power whilst also highlighting the ways in which Indigenous young people have navigated both disciplinary and normalising regimes. Fourteen participants (six male and eight female) were interviewed seven times over two and a half years using mapping, photos and drawing as stimuli. Data were analysed both thematically and through a process of discourse analysis with a view to explore the ways in which participants negotiated discursive constructions of the body, particularly notions of self-governance. It appeared that the young people engaged with, were ambivalent to, contested and resisted discourses around proper’ bodily appearance, the obligation to ‘work’ on their bodies, their perceptions of an ideal body, their negotiation of an authentic ‘black’ body and the ways in which they used their bodies to perform or achieve. The voices of the young people illustrate these themes. This research contributes significantly to the modest body of physical education and health literature from the perspectives of Indigenous young people. It raises questions about the impact of normalising discourses on Indigenous young people and in particular the ways in which those who resist them might be positioned