The synergistic effect of pimozide and romidepsin on a well-characterized MEITL PDX model. (A) Hematoxylin and eosin and immunohistochemical staining of subcutaneous MEITL PDX (P1, P3, and P6) and orthotopic (P3_IP) PDX tumors. (B) Venn diagrams of overlapping single-nucleotide variations (SNV, left) and indels (right) in a primary tumor (red) and a passage 3 subcutaneous tumor (blue). (C) Parabolic response surface maps of pimozide and romidepsin. (D) The combination index of romidepsin with the 20% inhibitory concentration (IC₂₀) of pimozide. ALCL, anaplastic large-cell lymphoma; ATL, acute T-cell leukemia. Data are means ± standard deviation of 3 independent biological replicates. (E) Immunoblots of indicated proteins in MEITL tumor cells treated with control (dimethyl sulfoxide), pimozide, romidepsin, and combination of the 2 drugs for 48 hours at the indicated concentrations. The experiments were repeated at least 3 times. (F) The MIETL PDX tumor growth curves. Treatment with 25 mg/kg pimozide combined with 1 mg/kg romidepsin significantly decreased tumor growth compared with pimozide or romidepsin alone or the vehicle control (n = 3). Error bars indicate standard error of the mean. *P < .05.