Fig. 1
From: Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models
Genetic landscapes of TCL models identify targetable vulnerabilities. a Mutational characteristics of the most recurrently altered genes in patients, PDX models and cell lines of different subtypes of T- and NK-cell lymphomas. Highlighted in red is the frequency of recurrent mutations in different subtypes of T- and NK-cell lymphomas, based on published sequencing studies (Supplementary Table 3) with n indicating the number of cases included. b GISTIC summary plots of the significant copy number gains (left panel, red) and losses (right panel, blue) in 20 T-cell lymphoma cell lines. Y-axis: chromosomal position, X-axis: false-discovery rate (FDR) q values. c A subset of selected fusions in PDX models and cell lines, identified by RNA-seq. d Immunoblotting in ALCL cell lines for the indicated targets. Wild-type JAK2 is approximately 130 kDa and PCM-JAK2 is approximately 260 kDa. e Copy number variants of JAK1 and JAK2 corresponding to d. f IC50 values for ruxolitinib corresponding to d. g Workflow of the ruxolitinib in vivo trial. h Spleens were harvested from mice treated with vehicle or ruxolitinib. Spleen weight, infiltration of the spleens by hCD45/hCD2+ cells and AnnexinV/7-AAD staining of vehicle vs ruxolitinib treated mice. Statistics: Unpaired two-sided t-test, * p < 0.05. i Immunoblotting of MAC2A cells treated in vitro with DMSO or 1 μM ruxolitinib for 24 h and DFTL-28776 treated in vivo with vehicle or ruxolitinib for 7 days. Bar graphs in f and i indicate mean values of at least two independent experiments with error bars indicating standard error of the mean
