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- W1567026817 abstract "Abstract : Systematic genomic discovery efforts in patients with bone marrow failure due to myelodysplastic syndrome (MDS) has led to the rapid discovery of recurrent somatic genetic alterations underlying these disorders. Remarkably, a large number of these mutations occur in genes whose function is known, or suspected, to be involved in epigenetic regulation of gene transcription. This includes mutations in ASXL1, TET2, and EZH2. The goals of our proposal were to (1) perform functional genetic characterization of these alterations, (2) determine if these alterations are therapeutically targetable, and (3) perform detailed genomic analysis of specific subsets of MDS patients with no known genetic alterations and with severe bone marrow failure to discover additional genetic alterations contributing to MDS pathogenesis. Since funding of this award we have made major progress in (1) understanding the impact of ASXL1 mutations and loss on chromatin (Abdel Wahab, et al. Cancer Cell 2012), (2) identifying the in vivo biological effects of deletion of Asxl1 and Tet2 alone and in combination with one another (Abdel- Wahab, et al. J Exp Med 2013), and (3) identified the genome- wide effects of Asxl1 on transcription (Abdel- Wahab, et al. J Exp Med 2013 and Abdel- Wahab, O, et al. Leukemia 2013). More recently we have identified that recently common mutations in the splicing machinery in MDS also may impact the function of these epigenetic modifiers (Kim, E, et al. Cancer Cell 2015)." @default.
- W1567026817 created "2016-06-24" @default.
- W1567026817 creator A5025595346 @default.
- W1567026817 date "2013-05-01" @default.
- W1567026817 modified "2023-09-26" @default.
- W1567026817 title "Understanding and Targeting Epigenetic Alterations in Acquired Bone Marrow Failure" @default.
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