Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2

TET2 is a close relative of TET1, an enzyme that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. The gene encoding TET2 resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies. Somatic TET2 mutations are frequently observed in myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes including chronic myelomonocytic leukaemia (CMML), acute myeloid leukaemias (AML) and secondary AML (sAML). We show here that TET2 mutations associated with myeloid malignancies compromise catalytic activity. Bone marrow samples from patients with TET2 mutations displayed uniformly low levels of 5hmC in genomic DNA compared to bone marrow samples from healthy controls. Moreover, small hairpin RNA (shRNA)-mediated depletion of Tet2 in mouse haematopoietic precursors skewed their differentiation towards monocyte/macrophage lineages in culture. There was no significant difference in DNA methylation between bone marrow samples from patients with high 5hmC versus healthy controls, but samples from patients with low 5hmC showed hypomethylation relative to controls at the majority of differentially methylated CpG sites. Our results demonstrate that Tet2 is important for normal myelopoiesis, and suggest that disruption of TET2 enzymatic activity favours myeloid tumorigenesis. Measurement of 5hmC levels in myeloid malignancies may prove valuable as a diagnostic and prognostic tool, to tailor therapies and assess responses to anticancer drugs.     

Sol-Gel Synthesized Adsorbents for Metal Separation

Introduction Noble nanostructured adsorbents are of emerging interest due to the ability to fabricate and control thechemical and physical properties of these materialsNumerous materials have been developed in attemptto separate metal ions from aqueous st…     

Initial sequencing and comparative analysis of the mouse genome

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.     

The relationship between the effect of endotoxin on inducible enzymes and biosynthetic activity in rat liver

Résumé Étude du mécanisme d'action de la cortisone. L'induction de tryptophane oxygénase hépatique peut être complètement abolie par l'injection d'endotoxine à un moment où la synthèse hormonale de l'ARN total n'est apparemment pas modifiée.     

Experimental ancylostomiasis in chickens: effect of various dose of infective Ancylostoma caninum larvae on their migration and distribution

White leghorn chickens, when infected with repeated doses of Ancylostoma caninum larvae, expel the larvae at a faster rate than when infected with a single dose. This suggests that the initial dose induces some resistance in the host. An initial dose of 1000 and 2000 larvae, followed by a 2nd dose of the same order, induces resistance in the alimentary tract causing the entire larval burden either to migrate to other tissues (organs) or to be expelled in 24 h.     

Evidence for synergism in steroid hormone-receptor association

Summary A number of glucocorticoids stimulated oestradiol binding to liver cytosol receptor; oestradiol activated glucocorticoid receptor association at a time when it reversed triamcinolone mediated increase in liver glycogen synthesis.These studies were supported by the DRGST (IMB 7570744), the INSERM (CL 7650014) and the CNRS (AI 03 1917).     

Influence of oral glucose feeding on endotoxin lethality in mice

Summary Prolonged feeding of physiological solutions of glucose (5%) by gavage did not protect against either endotoxin death or liver glycogen depletion in mice.Supported by grants from the INSERM (CL 76.5.001.4), the CNRS (03 7860) and the DGRST. Thanks are due to M. Philippe for technical assistance.Maitre de Recherche au CNRS, to whom all correspondance should be addressed.