TET2 converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) in DNA and is frequently mutated in myeloid ma-lignancies, including myeloproliferative neoplasms. Here we show that the level of 5-hmC is decreased in granulocyte DNA from myeloproliferative neoplasm patients with TET2 mutations compared with granulocyte DNA from healthy patients. Inhibition of TET2 by RNA interference decreases 5-hmC levels in both human leukemia cell lines and cord blood CD34 cells. These results confirm the enzymatic function of TET2 in human hematopoietic cells. Knockdown of TET2 in cord blood CD34 cells skews progenitor differentiation toward the granulo-monocytic lineage at the expense of lym-phoid and erythroid lineages. In addition, by monitoring in vitro granulomonocytic development we found a decreased granulocytic differentiation and an increase in monocytic cells. Our results indicate that TET2 disruption affects 5-hmC levels in human myeloid cells and participates in the pathogenesis of my-eloid malignancies through the disturbance of myeloid differentiation. (Blood. 2011;118(9):2551-2555)

International audiencePeripheral T-Cell lymphomas (PTCL) are relatively rare diseases but appear as highly aggressive and display worse remission and survival rates than B-cell lymphomas. Despite non satisfactory results with the CHOP regimen, it remains the reference front line therapy in these diseases, but has not been challenged in phase III trials. The GOELAMS group devised an alternative therapeutic schedule including Etoposide, Ifosfamide, Cisplatin alternating with Doxorubicin, Bleomycin, Vinblastin, Dacarbazine (VIP-reinforced-ABVD) and compared it to CHOP/21 as front-line treatment in non cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2-years event-free survival (EFS) rate. Secondary objectives were to compare the response rates, overall survival, and toxicities as well as identify prognostic factors. 88 patients were identified between 1996 and 2002. Both arms were well balanced for patients' characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2-years EFS. ALCL type and Ann Arbor stage I-II were identified as two independent favourable prognostic factors influencing survival. The VIP-rABVD regimen was not superior to CHOP/21 in term of EFS as first-line treatment of PTCL, confirming that CHOP/21 remains the reference arm in these lymphomas