Project leaflet: Summary about the ARIMMORA project published in the BEMS (Bioelectromagnetics Society) Newsletter No. 223.

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Publication: I. Liorni, M. Parazzini,S. Fiocchi, M. Douglas, M. Capstick, M.-C. Gosselin, N. Kuster, and P. Ravazzani, Dosimetric Study of Fetal Exposure to Uniform Magnetic Fields at 50 Hz. Bioelectromagnetics 2014, 35: 580–597.

Numerical modeling was used to analyze the exposure of fetuses at three different gestational ages (GA) to uniform magnetic fields at 50 Hz power line frequencies with different polarizations. Fetal whole-body and tissue-specific induced electric fields (E) and current densities (J) were analyzed as a function of both magnetic field polarization and GA. Particular emphasis was placed on choosing the tissue parameters used in the models, and a full survey of the relevant literature was performed. Induced field variations due to changes in fetal position were analyzed by means of two new pregnant models. The uncertainty budget due to the grid resolutionwas calculated, and the compliance of the fetal exposure with the ICNIRP Guidelines was checked. A fetal exposure matrix at 50 Hz, which could be used to further investigate possible interaction mechanisms between ELF-MF and health risk, was built. In summary, the induced fields increase with GA, but are in compliance with the ICNIRP Guidelines and well below the permitted threshold limit. The E and J maxima were found in skin and fat tissues for all GA; fetal tissue-specific exposure is modified as a function of GA and field polarization. Changes in the position of the fetus in the womb significantly modifies the induced E in some fetal tissues.

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Publication: Julia Hauer, Arndt Borkhardt, Isidro Sánchez-García, and César Cobaleda, Genetically engineered mouse models of human B-cell precursor leukemias. Cell Cycle 2014, 13: 2836–2846.

B-cell precursor acute lymphoblastic leukemias (pB-ALLs) are the most frequent type of malignancies of the childhood, and also affect an important proportion of adult patients. In spite of their apparent homogeneity, pB-ALL comprises a group of diseases very different both clinically and pathologically, and with very diverse outcomes as a consequence of their biology, and underlying molecular alterations. Their understanding (as a prerequisite for their cure) will require a sustained multidisciplinary effort from professionals coming from many different fields. Among all the available tools for pB-ALL research, the use of animal models stands, as of today, as the most powerful approach, not only for the understanding of the origin and evolution of the disease, but also for the development of new therapies. In this review we go over the most relevant (historically, technically or biologically) genetically engineered mouse models (GEMMs) of human pB-ALLs that have been generated over the last 20 years. Our final aim is to outline the most relevant guidelines that should be followed to generate an “ideal” animal model that could become a standard for the study of human pB-ALL leukemia, and which could be shared among research groups and drug

development companies in order to unify criteria for studies like drug testing, analysis of the influence of environmental risk factors, or studying the role of both low-penetrance mutations and cancer susceptibility alterations.

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Publication: Geoffrey Brown and Isidro Sánchez-García, Is lineage decision-making restricted during tumoral reprograming of haematopoietic stem cells? Oncotarget 2015, published online October 19, 2015

Within the past years there have been substantial changes to our understanding of haematopoiesis and cells that initiate and sustain leukemia. Recent studies have revealed that developing haematopoietic stem and progenitor cells are much more heterogeneous and versatile than has been previously thought. This versatility includes cells using more than one route to a fate and cells having progressed some way towards a cell type retaining other lineage options as clandestine. These notions impact substantially on our understanding of the origin and nature of leukemia. An important question is whether leukemia stem cells are as versatile as their cell of origin as an abundance of cells belonging to a lineage is often a feature of overt leukemia. In this regard, we examine the coming of age of the “leukemia stem cell” theory and the notion that leukemia, like normal haematopoiesis, is a hierarchically organized tissue. We examine evidence to support the notion that whilst cells that initiate leukemia have multi-lineage potential, leukemia stem cells are reprogrammed by further oncogenic insults to restrict their lineage decision-making. Accordingly, evolution of a sub-clone of lineage-restricted malignant cells is a key feature of overt leukemia./p>

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Summary of the first Periodic Report

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Summary of the second Periodic Report

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Summary of the third Periodic Report

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Summary of the Final Report

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Deliverable: 10.18 Report on awareness and wider societal implications

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