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Alpar, D.; Wren, D.; Ermini, L.; Mansur, M.B.; van Delft, F.W.; Bateman, C.M.; Titley, I.; Kearney, L.; Szczepanski, T.; de Castro, D.G.; Ford, A.M.; Potter, N.E.; Greaves, M. |
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Title |
Clonal origins of ETV6-RUNX1 acute lymphoblastic leukemia: studies in monozygotic twins |
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Journal Article |
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Year |
2014 |
Publication |
Leukemia |
Abbreviated Journal |
Leukemia |
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Studies on twins with concordant acute lymphoblastic leukemia (ALL) have revealed that ETV6-RUNX1 gene fusion is a common, pre-natal genetic event with other driver aberrations occurring subclonally and probably post-natally. The fetal cell type that is transformed by ETV6-RUNX1 is not identified by such studies or by the analysis of early B-cell lineage phenotype of derived progeny. Ongoing, clonal immunoglobulin (IG) and cross-lineage T-cell receptor (TCR) gene rearrangements are features of B-cell precursor leukemia and commence at the pro-B-cell stage of normal B-cell lineage development. We reasoned that shared clonal rearrangements of IG or TCR genes by concordant ALL in twins would be informative about the fetal cell type in which clonal advantage is elicited by ETV6-RUNX1. Five pairs of twins were analyzed for all varieties of IG and TCR gene rearrangements. All pairs showed identical incomplete or complete V(D)J junctions coupled with substantial, subclonal and divergent rearrangements. This pattern was endorsed by single cell genetic scrutiny in one twin pair. Our data suggest that the pre-leukemic initiating function of ETV6-RUNX1 fusion is associated with clonal expansion early in the fetal B-cell lineage.Leukemia accepted article preview online, 12 November 2014. doi:10.1038/leu.2014.322. |
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Centre for Evolution and Cancer, The Institute of Cancer Research – London, London, UK |
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0887-6924 |
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PMID:25388957 |
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CBM.UAM @ ccobaleda @ |
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542 |
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Alsaeed, I.; Al-Somali, F.; Sakhnini, L.; Aljarallah, O.S.; Hamdan, R.M.M.; Bubishate, S.A.; Sarfaraz, Z.K.; Kamal, A. |
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Title |
Autism-relevant social abnormalities in mice exposed perinatally to extremely low frequency electromagnetic fields |
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Journal Article |
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Year |
2014 |
Publication |
International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience |
Abbreviated Journal |
Int J Dev Neurosci |
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37 |
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58-64 |
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Keywords |
Anxiety; Autism spectrum disorder; Electromagnetic field; Motor coordination; Perinatal exposure; Social novelty |
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Abstract |
The incidence of autism spectrum disorders (ASD) has been rising, but the causes of ASD remain largely unidentified. Collective data have implicated the increased human exposure to electromagnetic fields (EMF) in the increasing incidence of ASD. There are established biological effects of extremely low-frequency (ELF) EMF, but the relation to ASD is not investigated enough. In this study we examined the effects of perinatal exposure to ELF EMF on some ASD-relevant behavioral parameters in mice. The EMF was delivered via a Helmholtz coil pair. Male BALB/C mice were used and divided into exposed and control groups (n=8 and n=9, respectively). Tests were used to assess sociability, preference for social novelty, locomotion, anxiety, exploratory behavior, motor coordination, and olfaction. The examined mice were all males and exposed to EMF during the last week of gestation and for 7 days after delivery. The exposed mice demonstrated a lack of normal sociability and preference for social novelty while maintaining normal anxiety-like behavior, locomotion, motor coordination, and olfaction. Exposed mice also demonstrated decreased exploratory activity. We concluded that these results are supportive of the hypothesis of a causal link between exposure to ELF-EMF and ASD; however, replications of the study with further tests are recommended. |
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Department of Physiology, College of Medicine and Medical Sciences, Arabian Gulf University, P.O. Box 26671, Manama, Bahrain. Electronic address: amerha@agu.edu.bh |
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0736-5748 |
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PMID:24970316 |
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CBM.UAM @ ccobaleda @ |
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589 |
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Baek, S.; Quan, X.; Kim, S.; Lengner, C.; Park, J.-K.; Kim, J. |
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Title |
Electromagnetic fields mediate efficient cell reprogramming into a pluripotent state |
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Journal Article |
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Year |
2014 |
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ACS nano |
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8 |
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10 |
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10125-10138 |
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Keywords |
arth has a magnetic; cell reprogramming; electromagnetic fi elds; epigenetic changes; fi eld that extends; from its inner core; protecting us from a; the solar wind; to where it meets |
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Life on Earth is constantly exposed to natural electromagnetic fields (EMFs), and it is generally accepted that EMFs may exert a variety of effects on biological systems. Particularly, extremely low-frequency electromagnetic fields (EL-EMFs) affect biological processes such as cell development and differentiation; however, the fundamental mechanisms by which EMFs influence these processes remain unclear. Here we show that EMF exposure induces epigenetic changes that promote efficient somatic cell reprogramming to pluripotency. These epigenetic changes resulted from EMF-induced activation of the histone lysine methyltransferase Mll2. Remarkably, an EMF-free system that eliminates Earth's naturally occurring magnetic field abrogates these epigenetic changes, resulting in a failure to undergo reprogramming. Therefore, our results reveal that EMF directly regulates dynamic epigenetic changes through Mll2, providing an efficient tool for epigenetic reprogramming including the acquisition of pluripotency. |
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WP5 In vitro |
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UNIBAS @ david.schuermann @ |
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546 |
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Brisdelli, F.; Bennato, F.; Bozzi, A.; Cinque, B.; Mancini, F.; Iorio, R. |
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Title |
ELF-MF attenuates quercetin-induced apoptosis in K562 cells through modulating the expression of Bcl-2 family proteins |
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Newspaper Article |
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2014 |
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Molecular and Cellular Biochemistry |
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33-43 |
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Apoptosis; Bcl-2; Elf-Mf; K562 cells; Quercetin |
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This study investigated the effects of sinusoidal ELF-MF (1 mT; 50 Hz) on the apoptosis induced by four different compounds, namely vinblastine, etoposide, quercetin, and resveratrol, in human K562 chronic myeloid leukemia cells. The exposure to ELF-MF did not affect growth and viability of untreated K562 cells and did not influence the anti-proliferative effects of resveratrol, vinblastine, and etoposide. On the contrary, in quercetin-treated cells, exposure to ELF-MF significantly reduced the percentage of apoptotic cells and the caspase-3 activity and modified the cell cycle profile especially after 48 h of exposure. In addition, the simultaneous treatments for 24 h with quercetin plus ELF-MF increased Bcl-2 protein expression and prevented quercetin-induced downregulation of Mcl-1 and Bcl-xL. Finally, an increase of HSP70 expression was also observed after prolonged ELF-MF treatment. The ELF-MF-dependent modulation of the expression of anti-apoptotic Bcl-2 family and Hsp70 proteins could act as a pro-survival mechanism in K562 cells. |
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UNIBAS @ david.schuermann @ |
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572 |
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Bunch, K.J.; Keegan, T.J.; Swanson, J.; Vincent, T.J.; Murphy, M.F.G. |
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Residential distance at birth from overhead high-voltage powerlines: childhood cancer risk in Britain 1962-2008 |
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Journal Article |
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Year |
2014 |
Publication |
British Journal of Cancer |
Abbreviated Journal |
Br J Cancer |
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110 |
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5 |
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1402-1408 |
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Adolescent; Case-Control Studies; Child; *Electromagnetic Fields; Environmental Exposure/adverse effects/*statistics & numerical data; Female; Great Britain/epidemiology; Humans; Leukemia/*epidemiology/etiology; Neoplasms/*epidemiology/etiology; Risk |
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BACKGROUND: We extend our previous study of childhood leukaemia and proximity to high-voltage powerlines by including more recent data and cases and controls from Scotland, by considering 132-kV powerlines as well as 275 and 400 kV and by looking at greater distances from the powerlines. METHODS: Case-control study using 53,515 children from the National Registry of Childhood Tumours 1962-2008, matched controls, and calculated distances of mother's address at child's birth to powerlines at 132, 275, and 400 kV in England, Wales and Scotland. RESULTS: Our previous finding of an excess risk for leukaemia at distances out to 600 m declines over time. Relative risk and 95% confidence interval for leukaemia, 0-199 m compared with>1000 m, all voltages: 1960s 4.50 (0.97-20.83), 2000s 0.71 (0.49-1.03), aggregate over whole period 1.12 (0.90-1.38). Increased risk, albeit less strong, may also be present for 132-kV lines. Increased risk does not extend beyond 600 m for lines of any voltage. CONCLUSIONS: A risk declining over time is unlikely to arise from any physical effect of the powerlines and is more likely to be the result of changing population characteristics among those living near powerlines. |
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Childhood Cancer Research Group, University of Oxford, New Richards Building, Old Road Campus, Headington, Oxford OX3 7LG, UK |
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0007-0920 |
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PMID:24504371 |
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CBM.UAM @ ccobaleda @ |
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582 |
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