TET2mutant

TET2mutant refers to cells or samples that carry pathogenic variants in the TET2 gene. TET2 encodes the ten-eleven translocation 2 enzyme, which participates in DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine and other oxidized forms. Most TET2 mutations are loss-of-function and can alter the activity of the TET2 protein, leading to changes in epigenetic marks and gene expression.

In hematopoietic cells, TET2 mutations can promote clonal expansion and skew differentiation, contributing to abnormal hematopoiesis. TET2mutant clones are among the most common somatic alterations in myeloid malignancies and are also frequently detected in age-related clonal hematopoiesis of indeterminate potential (CHIP). TET2 mutations often occur with other genetic changes, and the pattern of co-mutations can influence disease biology and clinical outcomes.

Clinical significance varies by disease context. TET2mutant status is used in molecular diagnostics and contributes to risk stratification in myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML), with prognostic impact dependent on disease subtype and co-occurring mutations such as DNMT3A, ASXL1, or RUNX1. Detection is typically achieved through targeted next-generation sequencing panels, with mutation type (frameshift, nonsense, missense, splice-site) and variant allele frequency informing clonal burden.

Therapeutic implications are context-dependent. Hypomethylating agents (e.g., azacitidine, decitabine) are standard for MDS and CMML, and some studies have reported favorable responses in TET2mutant cases, though results are not uniform. Ongoing research continues to clarify how TET2mutant status influences prognosis and treatment response across myeloid neoplasms.