By genetically modifying exosomes with two distinct types of surface-displayed monoclonal antibodies, we have developed an exosome platform termed synthetic multivalent antibodies retargeted exosome (SMART-Exo) for controlling cellular immunity. Due to their unique and pharmacologically important properties, cell-derived exosome nanoparticles have drawn significant interest for drug development. This study shed new lights into the ontogeny of JMML, and the identity of JMML-PCs, and provides robust models to monitor the disease and test novel therapeutic approaches.Įxosomes are nanosized membranous vesicles secreted by a variety of cells. We show that the hematopoietic stem/progenitor cell phenotype is globally maintained in JMML despite overexpression of CD90/THY-1 in a subset of patients. Further integrated analysis also reveals that although the mutations are acquired in hematopoietic stem cells, JMML-PCs are not always restricted to this compartment, highlighting the heterogeneity of the disease during the initiation steps. Combining genomic (exome, RNA-seq), Colony forming assay and xenograft studies, we detect the presence of JMML-PCs that faithfully reproduce JMML features including the complex/nonlinear organization of dominant/minor clones, both at diagnosis and relapse. Genomic analyses have recently described JMML mutational landscape however, the nature of JMML-propagating cells (JMML-PCs) and the clonal architecture of the disease remained until now elusive. Juvenile myelomonocytic leukemia (JMML) is a rare aggressive myelodysplastic/myeloproliferative neoplasm of early childhood, initiated by RAS-activating mutations.
That meant that he was excluded from a paternity test, but a DNA-based ancestry check showed that he was the child’s uncle.īut many people who have the condition will never take a paternity test for their children, or find out through other means. In the case of the Washington man reported this week, different genes were found in his cheek - where the saliva in the test was taken from - and his sperm. Her children were not genetically hers - and the real genetic mother was a twin sister that was never born. In previous cases, people have been found to have two different blood types, or to develop different sexual organs from those that would be associated with the rest of their body.Īnother example involved Karen Keegan, a woman from Boston in the US who had a different set of genes in her blood cells and her ovaries. And it may become yet more common, as more people use fertility treatments to conceive their children. The condition is relatively common in some animals - but it may happen more often than we realise in humans, and go unnoticed. That can lead to strange results in the DNA of people that have the condition - but it can often go completely unnoticed. The condition occurs when one unborn child absorbs the cells of another miscarried sibling in the womb, leading to the surviving person taking some of the genes of their “ghost” twin. Human chimerism hit the headlines this week after it was revealed that a man had failed a paternity test because he had the condition - which meant that the genetic father of his child was his unborn twin.
This article was first published online by The Independent (UK) on 27 October 2015.ĭoctors are finding more and more instances of human chimeras - a condition that might affect far more people than we realise. Human chimera: What the rare condition is, and why there might be many more people with it than we realised.
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