Role of TET2 mutations in myeloproliferative neoplasms

Abstract

Recently, 5-hydroxymethylcytosine (5-hmC), the 6th base of DNA, was discovered as the product of the hydroxylation of 5-methylcytosine (5-mC) by the ten-eleven translocation (TET) oncogene family members. One of them, TET oncogene family member 2 (TET2), is mutated in a variety of myeloid malignancies, including in 15% of myeloproliferative neoplasms (MPN s). Recent studies tried to gofurther into the biological and epigenetic function of TET2protein and 5-hmC marks in the pathogenesis of myeloidmalignancies. Although its precise function remains partially unknown, TET2 appears to be an important regulator of hematopoietic stem cell biology. In both mouse and human cells, its inactivation leads to a dramatic deregulation of hematopoiesis that ultimately triggers blood malignancies. Understanding this leukemogenic process will provide tools todevelop new epigenetic therapies against blood cancers. © 2011 Springer Science+Business Media, LLC.