TET2 Mutations as a Part of DNA Deficiency in MDS

Researchers conducted a study to investigate TET gene expression and identify factors which can modulate the impact of mutations on clinical phenotypes and prognosis of myelodysplastic syndromes (MDS). The results appeared in Blood Advances.

DNA/RNA-sequencing and 5-hmC data were collated from 1,665 patients with MDS and 91 controls. The results showed that irrespective of mutations, a significant fraction of MDS patients exhibited lower TET2 expression, while 5-hmC levels were not uniformly decreased. The researchers noted that in searching for factors explaining compensatory mechanisms, they discovered that TET3 was up-regulated in MDS and inversely correlated with TET2 expression in wild-type cases. They observed that while TET2 was reduced across all age-groups, TET3 levels were increased in a likely feedback mechanism induced by TET2 dysfunction.

“This inverse relationship of TET2 and TET3 expression also corresponded to the expression of L-2-hydroxyglutarate dehydrogenase, involved in agonist/antagonist substrate metabolism,” the researchers wrote of the results. “Importantly, elevated TET3 levels influenced the clinical phenotype of TET2-deficiency whereby the lack of compensation by TET3 (low TET3 expression) was associated with poor outcomes of TET2 mutant carriers.”