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Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation.
Mutational and epigenetic profiling of a large acute myeloid leukemia (AML) patient cohort revealed that IDH1/2-mutant AMLs display global DNA hypermethylation and a specificHypermethylation signature, suggesting a shared proleukemogenic effect. Expand
5-hmC–mediated epigenetic dynamics during postnatal neurodevelopment and aging
The mapped 5-hmC genome-wide in mouse hippocampus and cerebellum at three different ages allowed us to assess its stability and dynamic regulation during postnatal neurodevelopment through adulthood, and found developmentally programmed acquisition of 5-HMC in neuronal cells. Expand
Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine
- Chun-Xiao Song, Keith E. Szulwach, +16 authors Chuan He
- Biology, Medicine
- Nature Biotechnology
- 1 January 2011
This method uses the T4 bacteriophage β-glucosyltransferase to transfer an engineered glucose moiety containing an azide group onto the hydroxyl group of 5-hmC, a recently identified epigenetic modification present in substantial amounts in certain mammalian cell types. Expand
Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation.
An animal model of conditional Tet2 loss in the hematopoietic compartment that leads to increased stem cell self-renewal in vivo as assessed by competitive transplant assays is reported. Expand
TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis.
It is reported that inactivation of Tet2 in mouse perturbs both early and late steps of hematopoiesis including myeloid and lymphoid differentiation in a cell-autonomous manner, endows the cells with competitive advantage, and eventually leads to the development of malignancies. Expand
Dnmt3a is essential for hematopoietic stem cell differentiation
Using conditional ablation, it is shown that Dnmt3a loss progressively impairs hematopoietic stem cell differentiation over serial transplantation, while simultaneously expanding HSC numbers in the bone marrow. Expand
Dnmt3a Is Essential for Hematopoietic Stem Cell Differentiation
It is shown that Dnmt3a plays a specific role in permitting HSC differentiation, as in its absence, phenotypically normal but impotent stem cells accumulate and differentiation capacity is progressively lost. Expand
Recurrent Somatic TET2 Mutations in Normal Elderly Individuals With Clonal Hematopoiesis
Exome sequencing of three elderly females with clonal hematopoiesis, demonstrated by X-inactivation analysis, identified somatic TET2 mutations that were specific to individuals withClonal HematopOiesis without hematological malignancies and were associated with alterations in DNA methylation. Expand
Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial.
- D. Steensma, M. Baer, +8 authors H. Kantarjian
- Journal of clinical oncology : official journal…
- 10 August 2009
It is suggested that decitabine can be administered in an outpatient setting with comparable efficacy and safety to the United States Food and Drug Administration-approved inpatient regimen. Expand
Therapy-related myeloid leukemia.
A deeper understanding of the factors that predispose patients to the development of therapy-related myeloid leukemia would help clinicians monitor patients more carefully after treatment for a primary condition and could influence initial treatment strategies with the goal of decreasing the incidence of this serious complication. Expand