Laura Elisabet Gómez Sánchez

Epigenetic repression of ROR2 has a Wnt-mediated, pro-tumourigenic role in colon cancer

BackgroundWnt factors control cell differentiation through semi-independent molecular cascades known as the β-catenin-dependent (canonical) and -independent (non-canonical) Wnt signalling pathways. Genetic and epigenetic alteration of components of the canonical Wnt signalling pathway is one of the primary mechanisms underlying colon cancer. Despite increasing evidence of the role of the non-canonical pathways in tumourigenesis, however, the underlying molecular mechanisms are poorly understood.ResultsHere we report that the receptor tyrosine kinase-like orphan receptor 2 (ROR2), a transmembrane receptor for Wnt factors that activates non-canonical pathways, is frequently repressed by aberrant promoter hypermethylation in human colon cancer cell lines and primary tumours. By restoring ROR2 activity in colon cancer cells harbouring ROR2 promoter hypermethylation, we show that the role of ROR2 in colon cancer cells is mediated, at least in part, by canonical Wnt and that its epigenetic-dependent loss can be pro-tumourigenic.ConclusionsOur data show the importance of epigenetic alterations of ROR2 in colon cancer, highlighting the close interconnection between canonical and non-canonical Wnt signalling pathways in this type of tumour.

A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification.

The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute lymphoblastic leukemia in infants. Although it is well established that MLL-AF4 arises prenatally during human development, its effects on hematopoietic development in utero remain unexplored. We have created a human-specific cellular system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells (hESCs). Functional studies, clonal analysis and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. MLL-AF4 acts as a global transcriptional activator and a positive regulator of homeobox gene expression in hESCs. Functionally, MLL-AF4 enhances the specification of hemogenic precursors from hESCs but strongly impairs further hematopoietic commitment in favor of an endothelial cell fate. MLL-AF4 hESCs are transcriptionally primed to differentiate towards hemogenic precursors prone to endothelial maturation, as reflected by the marked upregulation of master genes associated to vascular-endothelial functions and early hematopoiesis. Furthermore, we report that MLL-AF4 expression is not sufficient to transform hESC-derived hematopoietic cells. This work illustrates how hESCs may provide unique insights into human development and further our understanding of how leukemic fusion genes, known to arise prenatally, regulate human embryonic hematopoietic specification.

Duelo en discapacidad intelectual: los avances de una década

The increased life expectancy in population with intellectual disability (ID) has revealed a lack of knowledge about grief in this group. For this reason, the present review tries to identify the advances made in the last decade in relation to the characteristics of the process of bereavement in people with ID, the available assessment tools and the main intervention models proposed in the field. To this end, a search for studies published from 2007 to 2017 was carried out in different databases. The results show peculiarities in the process, scarcity of specific assessment tools for this population and a lack of consensus on the type of intervention to be delivered. A discussion is raised about the importance of systematization in studies, use of tools that allow knowing people’s support needs with psychometric guarantees and the necessity of evidence-based practices.

Evaluating the characteristics of the grieving process in people with intellectual disability

BACKGROUND The aim of this study was to examine the characteristics associated with the grieving process among a population with intellectual disability and the influence of particular variables. MATERIALS AND METHODS The sample was composed of 380 participants with intellectual disability, on whose behalf 149 professionals completed a 20-item questionnaire with four Likert-type answer options, developed to evaluate the grieving process: Inventory of Grief and Coping Strategies in Intellectual Disability (IGCS-ID). RESULTS The IGCS-ID shows adequate levels of reliability. It covers three dimensions: understanding of the concept of death, coping with the loss and post-bereavement reactions. The level of intellectual disability, the time elapsed since the loss and the residential setting gave rise to significant differences in the three dimensions based on the participants. CONCLUSION An assessment of the grieving process would help to put in place effective resources to help people with intellectual disability overcome the loss and cope with the changes that it brings.

Síndrome de Down y enfermedad de Alzheimer: factores de riesgo, evaluación e intervención

Existe una estrecha relacion entre el sindrome de Down y la enfermedad de Alzheimer. Diversos factores de riesgo influyen en esta relacion, en la que la evaluacion de la demencia es dificil debido a la falta de instrumentos y tratamientos especificos. Se realizo una busqueda de los anos comprendidos entre 2005-2015 en diferentes bases de datos. Se identificaron diversos factores de riesgo (geneticos, ambientales, cognitivos) y se encontraron varios instrumentos de evaluacion, poco adecuados y/o con debilidades psicometricas. Los tratamientos existentes son escasos y, casi exclusivamente, farmacologicos. Se discute acerca de la importancia de llevar a cabo estudios sistematicos sobre los factores de riesgo para la prevencion de la enfermedad de Alzheimer en personas con sindrome de Down, asi como la necesidad de un protocolo de evaluacion especifico y adaptado que permita implementar tratamientos mas especificos y efectivos.