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Tet2 is required for Socs activation in immune response cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE122686 | GEO | 2020/12/31

REPOSITORIES: GEO

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Tet2 is required for Socs activation in immune response cells [RRBS]

Project description:Purpose: We have previously established an in vitro murine model that recapitulates the transformed phenotype of primary Tet2-/- mast cells expressing the Kit kinase domain mutant allele, D816V, that is both an oncogene and characterises patients with mastocytosis. To better understand the molecular basis of this cooperation and to further our understanding of role of Tet2 during inflammation and in other immune system disorders, we used this same in vitro primary cell system for genome wide studies to identify genes and genomic loci that are deregulated when these two mutations cooperate in mast cells.

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Tet2 is required for Socs activation in immune response cells [RNA-seq_mouse]

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Tet2 is required for Socs activation in immune response cells [RNA-seq_human]

Project description:Purpose: Systemic mastocytosis is a rare and chronic disease with phenotypes ranging from indolent to severe. Prognosis for this disease is variable and very few biomarkers to predict disease evolution or outcome are currently known. We have performed comprehensive screening in our large cohort of systemic mastocytosis patients for mutations previously found in other myeloid diseases and that could serve as prognostic indicators. KIT, SRSF2-P95 and TET2 mutations were by far the most frequent, detected in 81, 24 and 21 percent of patients, respectively. To understand the molecular mechanisms that regulate the functional cooperation that we and others have described for oncogenic KitD816V and Tet2 loss-of-function mutations in aggressive mastocytosis, and as part of a larger study, we have sequenced the transcriptomes of mast cells sorted from bone marrow biopsies of 3 patients in our cohort with aggressive disease and KitD816V mutation and 3 patients with aggressive disease, KitD816V and Tet2 mutation.

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Tet2 is required for Socs activation in immune response cells

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