SHP2 inhibition overcomes crizotinib resistance in ALK⁺ ALCL. (A-B) Western blot analysis performed on WT, PTPN1 KO, and PTPN2 KO JB6 cells treated with 80 nM of crizotinib and 1 or 5 μM of SHP099 in single or in combination for 1 hour. Cell lysates were blotted with indicated antibodies. One representative experiment out of 3 is shown. (C) Dose response curves of WT, PTPN1, and PTPN2 KO TS and JB6 cells incubated in increasing concentration of crizotinib in single or combination with SHP099 inhibitor at the indicated concentration for 72 hours. Data are represented as mean ± SD of technical triplicates; **P < .01, ****P < .0001, 2-way ANOVA followed by Dunnett's multiple comparisons test. (D-E) Combenefit synergy plot and Bliss Synergy Score of combined crizotinib and SHP099 in WT, PTPN1 KO, and PTPN2 KO TS (D), or JB6 (E) cell lines. Blue: synergy, green: additivity, and red: antagonism.