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“In the adult mammalian brain, neurogenesis from neural stem/progenitor cells continues in two regions: the subgranular zone in the dentate RepSox in vitro gyrus and the subventricular zone lining the lateral ventricles. The generated neuroblasts migrate to their appropriate location and differentiate to mature granule cells and olfactory bulb interneurons, respectively. Following injury such as stroke, neuroblasts generated in the subventricular zone migrate also into areas which are not normally neurogenic, e.g. striatum and cerebral cortex. In the initial

studies in rodents, brain inflammation and microglia activation were found to be detrimental for the survival of the new hippocampal neurons early after they had been born. The role of inflammation for adult neurogenesis has, however, turned out to be much more complex. Recent experimental evidence indicates that microglia under certain circumstances can be beneficial and support the different steps in neurogenesis, progenitor proliferation, survival, migration, and differentiation. Here we summarize the current knowledge on the role of inflammation and in particular of microglia in adult neurogenesis in the intact and injured mammalian brain. We conclude that microglia activation,

as an indicator of inflammation, is not pro- or antineurogenic per se but the net outcome is dependent on the balance between secreted molecules with pro- and antiinflammatory selleck products action. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Episomes with the NUP214-ABL1 fusion gene have been observed in 6% of T-ALL. In this multicentric study we collected 27 cases of NUP214-ABL1-positive T-ALL. Median age was 15 years with

male predominance. Outcome was poor in 12 patients. An associated abnormality involving TLX1 or TLX3 ADAM7 was found in all investigated cases. Fluorescent in situ hybridization revealed a heterogeneous pattern of NUP214-ABL1 amplification. Multiple episomes carrying the fusion were detected in 24 patients. Episomes were observed in a significant number of nuclei in 18 cases, but in only 1-5% of nuclei in 6. In addition, intrachromosomal amplification (small hsr) was identified either as the only change or in association with episomes in four cases and two T-ALL cell lines (PEER and ALL-SIL). One case showed insertion of apparently nonamplified NUP214-ABL1 sequences at 14q12. The amplified sequences were analyzed using array-based CGH.

These findings confirm that the NUP214-ABL1 gene requires amplification for oncogenicity; it is part of a multistep process of leukemogenesis; and it can be a late event present only in subpopulations. Data also provide in vivo evidence for a model of episome formation, amplification and optional reintegration into the genome. Implications for the use of kinase inhibitors are discussed.