Role of TET2 Mutations in Myeloproliferative Neoplasms
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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 (MPNs). Recent studies tried to go further into the biological and epigenetic function of TET2 protein and 5-hmC marks in the pathogenesis of myeloid malignancies. 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 to develop new epigenetic therapies against blood cancers.
KeywordsTET2 Mutations 5-hydroxymethylcytosine Myeloproliferative neoplasms Myeloid malignancies Hematopoietic stem cells Epigenetics Pathogenesis
The authors are grateful to the MPN research foundation, the Fondation de France, the Institut National du Cancer, the Ligue Nationale Contre le Cancer, the Association pour la Recherche sur le Cancer, and the French Ministry of Research.
No potential conflicts of interest relevant to this article were reported.
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