منابع مشابه
TET2 loss, a rescue of JAK2V617F HSCs.
In this issue of Blood, Chen et al and Kameda et al demonstrate that Tet2 loss has 2 effects in Jak2V617F mice: it increases both the severity of the myeloproliferative disorders and the self-renewal properties of the Jak2V617F hematopoietic stem cells (HSCs).
متن کاملGene expression profiling of loss of TET2 and/or JAK2V617F mutant hematopoietic stem cells from mouse models of myeloproliferative neoplasms
Myeloproliferative neoplasms (MPNs) are clinically characterized by the chronic overproduction of differentiated peripheral blood cells and the gradual expansion of malignant intramedullary/extramedullary hematopoiesis. In MPNs mutations in JAK2 MPL or CALR are detected mutually exclusive in more than 90% of cases [1,2]. Mutations in them lead to the abnormal activation of JAK/STAT signaling an...
متن کاملLoss of TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator.
Acquired mutations of JAK2 and TET2 are frequent in myeloproliferative neoplasms (MPNs). We examined the individual and cooperative effects of these mutations on MPN development. Recipients of JAK2V617F cells developed primary myelofibrosis-like features; the addition of loss of TET2 worsened this JAK2V617F-induced disease, causing prolonged leukocytosis, splenomegaly, extramedullary hematopoie...
متن کاملTet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells
TET2 is a dioxygenase that catalyses multiple steps of 5-methylcytosine oxidation. Although TET2 mutations frequently occur in various types of haematological malignancies, the mechanism by which they increase risk for these cancers remains poorly understood. Here we show that Tet2-/- mice develop spontaneous myeloid, T- and B-cell malignancies after long latencies. Exome sequencing of Tet2-/- ...
متن کاملTET2 Loss Dysregulates the Behavior of Bone Marrow Mesenchymal Stromal Cells and Accelerates Tet2−/−-Driven Myeloid Malignancy Progression
TET2 is a methylcytosine dioxygenase that regulates cytosine hydroxymethylation. Although there are extensive data implicating a pivotal role of TET2 in hematopoietic stem/progenitor cells (HSPCs), the importance of TET2 in bone marrow mesenchymal stromal cells (BMSCs) remains unknown. In this study, we show that loss of TET2 in BMSCs increases cell proliferation and self-renewal and enhances o...
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ژورنال
عنوان ژورنال: Blood
سال: 2015
ISSN: 0006-4971,1528-0020
DOI: 10.1182/blood-2014-10-606624