The response of chimeric proteins to ATRA. (A) PML::RARA, bipartite PML::RARA fusion with intact LBD. PML::RARA-delH12, simulated PML::RARA fusion with artificial truncation of LBD helices 12 (LBD-H12) without a 3′ fusion partner. (B) STAT3::RARA, simulated bipartite STAT3::RARA fusion with intact LBD. STAT3::RARA::LTR40a, tripartite STAT3::RARA::LTR40a fusion as identified in index case A1. (C) STAT5B::RARA, simulated bipartite STAT5B::RARA fusion with intact LBD. STAT5B::RARA::AluSx4, tripartite STAT5B::RARA::AluSx4 fusion as identified in case A8. (D) HNRNPC::RARA, simulated bipartite HNRNPC::RARA fusion with intact LBD. HNRNPC::RARA::HNRNPC, tripartite HNRNPC::RARA::HNRNPC fusion as identified in case A11. (E) NPM1::RARG, simulated bipartite NPM1::RARG fusion with intact LBD. NPM1::RARG::NPM1, tripartite NPM1::RARG::NPM1 fusion as identified in index case G1. NPM1::RARG-delH11_12, simulated NPM1::RARG fusion with artificial truncation of LBD-H11_12 without a 3′ fusion partner. (F) CPSF6::RARG, simulated bipartite CPSF6::RARG fusion with intact LBD. CPSF6::RARG::LINE-L2a, tripartite CPSF6::RARG::LINE-L2a fusion as identified in case G9. CPSF6::RARG-delH11_12, simulated CPSF6::RARG fusion with artificial truncation of LBD-H11_H12 without a 3′ fusion partner. (G) HNRNPC::RARG, simulated bipartite HNRNPC::RARG fusion with intact LBD. HNRNPC::RARG::HNRNPC, tripartite HNRNPC::RARG::HNRNPC fusion as in case G3. HNRNPC::RARG-delH11_12, simulated HNRNPC::RARG fusion with artificial truncation of LBD-H11_H12 without a 3′ fusion partner. These results demonstrate that all bipartite chimeric proteins with intact LBD exhibit a dose-dependent response to ATRA, whereas those with LBD-H11_12/H12 truncation displayed minimal to no response. The experiments were performed using a GAL4-UAS reporter system and 293T cell line. Results are presented as the mean ± standard deviation of 3 biological replicates. Statistical analysis was performed using analysis of variance with Tukey correction for multiple comparisons. A representative experiment out of 3 with similar results is displayed.