24 research outputs found

    EPMA position paper in cancer: current overview and future perspectives

    Get PDF

    NG2 antigen is involved in leukemia invasiveness and central nervous system infiltration in MLL-rearranged infant B-ALL

    Get PDF
    Mixed-lineage leukemia (MLL)-rearranged (MLLr) infant B-cell acute lymphoblastic leukemia (iMLLr-B-ALL) has a dismal prognosis and is associated with a pro-B/mixed phenotype, therapy refractoriness and frequent central nervous system (CNS) disease/relapse. Neuron-glial antigen 2 (NG2) is specifically expressed in MLLr leukemias and is used in leukemia immunophenotyping because of its predictive value for MLLr acute leukemias. NG2 is involved in melanoma metastasis and brain development; however, its role in MLL-mediated leukemogenesis remains elusive. Here we evaluated whether NG2 distinguishes leukemia-initiating/propagating cells (L-ICs) and/or CNS-infiltrating cells (CNS-ICs) in iMLLr-B-ALL. Clinical data from the Interfant cohort of iMLLr-B-ALL demonstrated that high NG2 expression associates with lower event-free survival, higher number of circulating blasts and more frequent CNS disease/relapse. Serial xenotransplantation of primary MLL-AF4+ leukemias indicated that NG2 is a malleable marker that does not enrich for L-IC or CNS-IC in iMLLr-B-All. However, NG2 expression was highly upregulated in blasts infiltrating extramedullar hematopoietic sites and CNS, and specific blockage of NG2 resulted in almost complete loss of engraftment. Indeed, gene expression profiling of primary blasts and primografts revealed a migratory signature of NG2+ blasts. This study provides new insights on the biology of NG2 in iMLLr-B-ALL and suggests NG2 as a potential therapeutic target to reduce the risk of CNS disease/relapse and to provide safer CNS-directed therapies for iMLLr-B-ALL.This work was supported by the European Research Council (CoG-2014-646903) and the Spanish Ministry of Economy-Competitiveness (SAF-SAF2013-43065) to PM, the Asociación Española Contra el Cáncer to CB and the ISCIII/FEDER (PI14/01191-PI13/00168) to CB and JCRM. PM acknowledges the financial support from the Obra Social La Caixa-Fundaciò Josep Carreras, the Inocente-Inocente Foundation and Generalitat de Catalunya. CP and DRM were funded by PFIS scholarships from the ISCIII. VA has financial support from L’Oreal-UNESCO. PM is investigator of the Spanish Cell Therapy cooperative network (TERCEL). We thank Antonio Agraz/Ignacio Varela (IBBTEC, Santander) for assisting in microarray analysis. We also thank Dr Patricia Pérez-Galán and Gael Roue (IDIBAPS, Barcelona, Spain) for helpful discussions on NG2 blocking experiments

    Clonal architecture in an intertidal bed of the dwarf eelgrass Zostera noltii in the Northern Wadden Sea: persistence through extreme physical perturbation and the importance of a seed bank

    Get PDF
    Genotypic structure and temporal dynamics of the dwarf seagrass, Zostera noltii, were studied in an intertidal meadow that has persisted since prior to 1936 near the Wadden Sea island of Sylt. Samples were collected from two 10 × 10 m plots separated by 250 m from May 2002 to June 2005 and from four 1 × 1 m plots from June 2003 to September 2004. All the samples were genotyped with nine microsatellite loci. No genotypes were shared between the plots separated by 250 m. Genetic diversity was higher in the Wadden Sea than in the other regions of its geographic range. The average clone size (genets) (SD) in the two plots was 1.38 (0.26) and 1.46 (0.4) m², respectively, with a range up to 9 m² and <20% persisted for >4 years. A high genetic and genotypic diversity was maintained by annual recruitment of seedlings despite a dramatic decrease in ramet density that coincided with the severe heat stress event of 2003. Fine-scale (1 m²) analysis suggested that extensive loss of seagrass cover precluded space competition among the genets, while a persistent seed bank prevented local extinction. Long-term persistence of Z. noltii meadows in the intertidal Wadden Sea was achieved by high genet turnover and frequent seedling recruitment from a seed bank, in contrast to the low diversity observed in large and long-living clones of Z. noltii and other seagrasses in subtidal habitats

    The status of hard coral communities at Kosrae, Micronesia

    No full text
    Coral diversity is increasingly threatened by multiple anthropogenic and climate stressors. Threatened species assessments play an important role in guiding conservation action for management and mitigation of losses, but to provide accurate assessments it is necessary to collect quantitative data at an appropriate scale. When assessed at a global scale the level of threat facing corals in the tropical western Pacific Ocean is perceived to be low. However, whether the global threat classifications reflect the needs of species at regional scales remains to be verified. Here the status of scleractinian coral diversity is explored at a little-known Micronesian locality, Kosrae (5°15’S 162°58 E). Sixteen percent of the species recorded on the current survey are classified as Vulnerable on a global scale; however, down-scaling the assessment suggests that a larger proportion of species (up to 25%) may be vulnerable to regional extinction because they occupy a low proportion of sites. Twelve species are classified as Vulnerable at global and regional scales, and further monitoring of threatened species is needed to verify the status of 53 species that are listed as Data Deficient in the region. Despite the lower level of perceived extinction risk to coral communities in the NW Pacific, this study suggests the risk of regional diversity loss may be higher than expected. Ongoing coral reef monitoring and integrated watershed management to mitigate the threat of regional extinctions is needed

    Temporal variation of intertidal seagrass in southern China (2008–2014)

    No full text
    Understanding the temporal dynamics of seagrasses and the major influences on seagrass growth is critical for seagrass habitat conservation and administration. However, little work has been done regarding these issues in southern China. To examine inter-annual and seasonal variations of the intertidal Halophila ovalis community in southern China, we conducted quarterly sampling using the SeagrassNet methodology and assessed environmental conditions as well as direct anthropogenic impacts on the seagrass meadow from July 2008 to October 2014. Our study demonstrated strong inter-annual and seasonal dynamics of the intertidal seagrass meadow in the study area. Generally, the community performed best (highest seagrass cover, leaf area, shoot density, total biomass) in summer and worst in spring among the 4 seasons. The temporal variations in the seagrass community attributes (e.g. above-ground biomass) were significantly affected by precipitation, atmospheric visibility, and salinity, while leaf width was significantly negatively correlated with temperature, atmospheric visibility and salinity. Temperature was a major factor influencing the seagrass community (both macroalgae and seagrass), with temperature data showing an inverse relationship between seagrass and macroalgae. The above-ground: below-ground biomass ratio and leaf width of H. ovalis were the most sensitive plant parameters monitored when assessing environmental interactions. Human physical disturbances did not have a significant effect on seagrass dynamics in the study area. We concluded that long-term monitoring (like SeagrassNet) is valuable in understanding the relationship between environmental variables and seagrasses
    corecore