Eltrombopag (TPO-R agonism) and selective TET2-mutant clone suppression
Current understanding
Eltrombopag, a small-molecule thrombopoietin receptor (MPL) agonist, is hypothesized to both stimulate residual normal hematopoiesis and preferentially suppress the growth of TET2-mutant clones in low-risk MDS and CMML. The mutation-selective cytoreductive effect is a novel proposed mechanism currently supported only by early-phase clinical investigation (trial-early evidence), with the molecular basis for TET2-clone selectivity not yet established.