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TET2 is an enzyme that helps erase methyl marks from DNA so genes can be switched back on. Losing it is one of the commonest first steps toward blood cancer; mutant IDH blocks it indirectly, which is part of how ivosidenib works when it restores normal maturation.
TET2 (chromosome 4q24) is a dioxygenase that converts 5-methylcytosine to 5-hydroxymethylcytosine and on to 5-formylcytosine and 5-carboxylcytosine, the first steps of active DNA demethylation, and also recruits the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes (UniProt Q6N021). The clonal-haematopoiesis pathway record lists TET2 with DNMT3A and ASXL1 among the mutations of clonal haematopoiesis of indeterminate potential, present in more than a tenth of people over 70 and progressing to myeloid neoplasm at about 0.5 to 1% a year. In OnCo it appears as the enzyme that 2-hydroxyglutarate from mutant IDH1 inhibits, so that ivosidenib restores TET2-dependent demethylation and differentiation, and as a mutation of the follicular helper T-cell lymphomas in which romidepsin is active.
In plain words · TET2 is an enzyme that helps erase methyl marks from DNA so genes can be switched back on. Losing it is one of the commonest first steps toward blood cancer; mutant IDH blocks it indirectly, which is part of how ivosidenib works when it restores normal maturation.
TET2 is an enzyme that helps erase methyl marks from DNA so genes can be switched back on. Losing it is one of the commonest first steps toward blood cancer; mutant IDH blocks it indirectly, which is part of how ivosidenib works when it restores normal maturation.
Mutant IDH1 converts alpha-ketoglutarate to the oncometabolite 2-hydroxyglutarate, TET2 and histone demethylases lose activity, and blasts stop maturing; ivosidenib shuts off 2-HG production and TET2 regains activity (ivosidenib mechanism steps).
No product in this corpus aims at TET2 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
First described 2000. Earliest sequence paper UniProt cites for the protein: Nagase et al, DNA Res, 2000, "Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". Source.
Mutant IDH1 converts alpha-ketoglutarate to the oncometabolite 2-hydroxyglutarate, TET2 and histone demethylases lose activity, and blasts stop maturing; ivosidenib shuts off 2-HG production and TET2 regains activity (ivosidenib mechanism steps). TET2 itself has no drug in the corpus.
Query for this target: (TITLE:"TET2" OR ABSTRACT:"TET2" OR TITLE:"KIAA1546" OR ABSTRACT:"KIAA1546" OR TITLE:"tet methylcytosine dioxygenase 2" OR ABSTRACT:"tet methylcytosine dioxygenase 2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about TET2, not a curated reading list.
Shares Epigenetic reprogramming, Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET) and the tag wave5-target.
Shares Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Acute myeloid leukaemia, Non-Hodgkin lymphoma (all types) and the tag wave5-target.
Shares Acute myeloid leukaemia, Non-Hodgkin lymphoma (all types) and the tag wave5-target.
Shares Epigenetic reprogramming, Acute myeloid leukaemia and the tag wave5-target.
Shares Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Non-Hodgkin lymphoma (all types) and the tag wave5-target.
Shares Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Non-Hodgkin lymphoma (all types) and the tag wave5-target.
Shares Acute myeloid leukaemia and the tag wave5-target.
Shares Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma) and the tag wave5-target.