Extended Data Fig. 4: CXCdel lymphoma cells are depleted upon inhibitor withdrawal.

a, Stacked bar plot showing the observed frequencies for out-of-frame, in-frame and no indels in the cDNA encoding EZH2 at week 6 in Karpas-422 and Pfeiffer cells transduced with sgA596/D597, sgD597/H598 or sgD597 under vehicle, GSK343 (1 μM) or EED226 (1 μM) treatment. b, Bar chart showing frequency of insertions or deletions of amino acids in the cDNA encoding EZH2 at week 6 in Karpas-422 transduced with sgD597 under vehicle treatment. Deletions, no change and insertions are shown by red, yellow and blue backgrounds respectively. c, Same as b. but for sgA596/D597 transduction in Karpas-422 under vehicle treatment. d, Same as b. but for sgD597/H598 transduction in Karpas-422 under vehicle treatment. e, Same as b. but for sgD597 transduction in Pfeiffer under vehicle treatment. f, Same as b. but for sgA596/D597 transduction in Karpas-422 under GSK343 (1 μM) treatment. g, Same as b. but for sgD597/H598 transduction in Karpas-422 under GSK343 (1 μM) treatment. h, Same as b. but for sgD597/H598 transduction in Karpas-422 under EED226 (1 μM) treatment. i, Same as b. but for sgD597 transduction in Pfeiffer under EED226 (incremental doses up to 500 nM) treatment. j, Schematic showing genotypes and bar plots of allele frequencies for mutations that are observed at frequencies of >2% in the cDNA encoding EZH2 encompassing the CXC and SET domains for GSK343 treatment at week 6 for sgD597 transduction in Karpas-422. Allele frequencies in the (blue) wild-type allele and (red) Y646N allele. (Top) Schematic depicts the secondary structure of C-terminal CXC ___domain and cysteine residues that coordinate the zinc ions. k, Same as in j. but for sgA596/D597 transduction in Karpas-422. l, Same as in j. but for sgD597 transduction in Pfeiffer. The wild-type allele is shown in blue and the A682G allele is shown in red. Data in a–l are represented by mean ± s.e.m of n = 3.

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