Second-generation TPO-RAs (romiplostim, eltrombopag, and avatrombopag) that overcome the immunogenicity of first-generation agents that generated neutralizing antibodies cross-reactive with endogenous TPO Splicing factor mutations are critical determinants of TPO-RA responsiveness in LR-MDS with thrombocytopenia; SRSF2 mutations significantly predict romiplostim response, occurring in 41% of responders versus 16% of non-responders, with patients harboring SRSF2 mutations achieving 65% response rates compared to 33% in wild-type patients [32]. The gene discussed is TPO; the disease is myelodysplastic syndrome.