Tet methylcytosine dioxygenase 2 (TET2) is a human gene. [5] It resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies.

Small interfering RNA (siRNA)-mediated TET2 knockdown (KD) increases LNCaP cell proliferation, migration, and wound healing, verifying loss drives a cancer phenotype. Endogenous TET2 bound the androgen receptor (AR) and AR-coactivator proteins in LNCaP cell extracts, and TET2 KD increases prostate-specific antigen (KLK3 /PSA) expression.

Here, we review the structure and function of TET2, its interactions with cooperating mutations and small molecules, and its role in aberrant hematopoiesis. The TET2 enzyme is a critical regulator of DNA methylation, which is important in cellular proliferation and differentiation.

Somatic mutations in TET2 are observed in the bone marrow of 5%–10% of healthy adults over 65 years of age, imparting a hematopoietic stem cell advantage and subsequent clonal hematopoiesis of indeterminate potential (CHIP), a condition which is associated with increased risk of myeloid malignancy.

TET2 is considered a tumor suppressor gene, and its haploid deficiency can initiate myeloid and lymphatic transformation. TET2 mutations, such as deletion, insertion, and code shift mutations, are usually accompanied by a significant reduction in the total amount of 5 hmC.

Oct 1, 2023 · The Km value of Tet1 and Tet2 for O 2 is 30 µm [77]. It could be suggested that this effect is probably not directly related to the repression of enzyme activity, but to the regulation of enzyme expression.

Nov 12, 2020 · Tet2-KO mice recapitulate characteristics of patients with myeloid cancer, indicating that Tet2 plays a functional role as a tumor suppressor to sustain hematopoietic cell homeostasis.

Oct 13, 2020 · TET2 oxidizes methylated cytosines to further modify cytosines, which behave as intermediates in active/passive DNA demethylation processes. TET2 itself associates with histone modifiers, thereby regulating histone modifications and expression of target genes.

Mar 27, 2019 · To investigate TET2’s role in PCa pathogenesis, we generated TET2 knockout (KO) cell-lines in representative normal prostate cells to discover key candidate genes regulated by TET2-mediated methylation reprogramming.

TET2 is highly expressed in hematopoietic stem/progenitor cells, and the deletion of TET2 in primary bone marrow cells leads to the increase of the percentage of immature c-Kit + Lin − cells, suggesting that loss of TET2 may affect stem/progenitor cell differentiation (4, 22).