Figure 5.

Schematic representation of TETi mechanism of action. TET2 mutant and TET-dixoygenase deficient cells are susceptible to further TET-inhibition. Loss to TET2 increases C→T transition and mutator phenotype leading to neoplastic evolution. Residual TET-dioxygenase activity from TET1 and TET3 in TET2 mutant cells are important for efficient transcription of survival and proliferative genes. Inhibition the residual TET-dioxygenase activity leads to preferential growth restriction and finally elimination of TET2 mutant and TET-dioxygenase deficient clones.