T-PLL–specific drug response. (A) Differential drug sensitivity of T-PLL (n = 6) compared with chronic lymphocytic leukemia (CLL; n = 27) samples in screen A. The x-axis shows the average difference in viability; negative values indicate higher sensitivity in T-PLL than in CLL. The y-axis shows the −log₁₀P value. For each drug, the average across all concentrations was tested. Top associations are labeled, if the difference in viability was >.05 and the P value <.05, as well as representatives of their drug class. Corresponding plots for screen B (8 T-PLL and 124 CLL samples) (B) and screen D (10 T-PLL and 275 CLL samples) (C). (D) Heat map showing the difference in drug response of MCL (n = 15), T-PLL (n = 12), T-LGL (n = 3), PTCL (n = 2), and Sézary lymphoma (n = 4) samples compared with that of CLL (n = 10) samples in screen E (supplemental Methods). Drug response between diagnosis groups was compared via a t test (null hypothesis: no difference), and 2-sided P values were computed. Hues of the color scale indicate raw P values (red: less, blue: more sensitive than CLL). Values are shown for the 5 highest concentrations (1, highest; 5, lowest). (E) Box plots showing the mean viability (averaged over all concentrations) for CLL (n = 10), MCL (n = 15), T-PLL (n = 12), T-LGL (n = 3), PTCL (n = 2), Sézary (n = 4), and 1 AITL sample after treatment with birinapant, selinexor, bafilomycin A1, and nutlin-3a. Each dot is a patient, observations outside the plotting range are censored and shown as triangles. (F) Dose response curve, showing the viability of T-PLL (n = 12) and other T-cell lymphoma (n = 10) samples after treatment with birinapant across 10 concentrations, normalized to a DMSO negative control. Each line indicates 1 patient. (G) Drug-drug correlation matrix for each pair of drugs used in screen E. The Pearson correlation coefficient (R²) was computed from the viabilities of the 12 T-PLL and 10 T-cell lymphoma samples after drug treatment (averaged over all concentrations). The rows and columns were arranged based on hierarchical clustering. Key correlation pairs are indicated by color. (H) Correlation plots show the viability (averaged over all concentrations) after birinapant treatment and GDC-0152, ruxolitinib, fludarabine, venetoclax, dacinostat, and nutlin-3a in 12 T-PLL and 10 T-cell lymphoma samples. A trendline is indicated; 95% confidence intervals are shown as shaded gray areas. Avg., average; AITL, angioimmunoblastic T-cell lymphoma; NHL, non-Hodgkin lymphoma; p.adj., adjusted P value; PTCL, peripheral T-cell lymphoma.