title: Perturbations of 5-hydroxymethylcytosine patterning in hematologic malignancies.
abstract: The recent identification of covalent cytosine modifications derived from the metabolism of 5-methylcytosine (5-mC) and catalyzed by the TET proteins has facilitated molecular insight into a new subclass of acute myeloid leukemias (AMLs). TET2-mutant AMLs have the predicted hypermethylation phenotype expected given the inability of the mutant TET2 protein to convert 5-mC to 5-hydroxymethylcytosine (5-hmC). In addition, IDH1/2 mutations confer a gain-of-function, allowing the enzymes to process α-ketoglutarate to 2-hydroxyglutarate, which inhibits the TET proteins and ultimately induces the same hypermethylation phenotype. New techniques are being developed rapidly that have the unprecedented capacity to distinguish among the various covalent cytosine modifications now known to exist. Soon, these methods will be harnessed to yield a new level of insight into AMLs with altered distribution of 5-hmC, information that may allow new diagnostic and therapeutic approaches for patients with this subtype of AML.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637-1470, USA.
authors.forename: Jozef
authors.initials: J
authors.lastname: Madzo
authors.forename: Aparna
authors.initials: A
authors.lastname: Vasanthakumar
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Godley
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D003596:Cytosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D019337:Hematologic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D007521:Isocitrate Dehydrogenase