Figure 5.

Schematic representation of TETi mechanism of action. TET2-mutant and TET dioxygenase–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 is important for efficient transcription of survival and proliferative genes. Inhibition of the residual TET dioxygenase activity leads to preferential growth restriction and finally elimination of TET2-mutant and TET dioxygenase–deficient clones.