Extended Data Fig. 2: Sensitivity of leukaemia and lymphoma cancer subtypes to complex II disruption.
a) Effect of Complex II inhibitor 3NP (2 mM) on viability of select cell lines that are either sensitive or resistant to TTFA. b) Differential effect of Complex II inhibition by TTFA on ATP levels (grey bars) assayed after 30 minutes compared to viability (black squares) recorded after 3 days in culture with TTFA (viability values used from experiments in Fig. 2a). Data in (a-b) show mean ± s.e.m. from n = 3 independent experiments. c) Complex II sub-lineage dependencies in cancer. Horizontal bars represent ranges of dependency scores for cancer sub-lineages, with differential Complex II dependency indicated by solid blue versus transparent gray bars. Shades of blue or gray within each bar represent the proportion of cells with a given dependency score interval, annotating 5%, 50% and 95% of cells within each sub-lineage (indicated in the legend as ‘level’). Leukemia and lymphoma subtypes with dependency scores that are significantly different from the aggregate of other sub-lineages are shown with arrows (Alk+ ALCL, Alk+ anaplastic large cell lymphoma; B-ALL/B-LLy, B-cell acute lymphoblastic leukemia/B-cell lymphoblastic lymphoma; DLBCL, diffuse large B-cell lymphoma; Bcr-Abl1+ CML, Bcr-Abl1+ chronic myeloid leukemia; AML, acute myeloid leukemia). d) Sdhb gene expression in the MLL-AF9 AML murine model after doxycycline induction of non-targeting (shNT) or Sdhb-targeting (Sdhb.1, Sdhb.2) small hairpin RNAs. Data show mean ± s.e.m. from n = 4 independent experiments. P values were calculated using a one-way ANOVA with a Tukey’s post-hoc test.
