Extended Data Fig. 9: Divergent drug responses in a STAT5- and ERK-driven pair of primary and relapse B-ALLs.

a, c–d, LAX7 (at diagnosis; STAT5-driven, IL7R^SI246S) and LAX7R (relapsed; ERK-driven, KRAS^G12V) cells were transfected with Cas9/RNPs carrying NT or BLNK guide RNAs and then mixed with GFP⁺ LAX7 and GFP⁺ LAX7R competitor cells, respectively. a, d, Enrichment or depletion of GFP⁺ cells was monitored by flow cytometry (n = 3 independent experiments). Data are means ± s.d. (note that the direction of the y-axis in a is reversed, starting from a fold change of 2.5 at the bottom). b, Levels of ERK1/2-pT202/Y204, ERK1/2, STAT5-pY694 and STAT5 in patient-derived B-ALL cells (IL7R^SI246S LAX7, at diagnosis; KRAS^G12V LAX7R, relapsed) were examined by western blotting (n = 3 independent experiments, shown are two of the technical replicates from an independent experiment). c, Efficiency of CRISPR/Cas9-mediated deletion of BLNK was assessed by western blot (crRNAs, CRISPR RNAs). e, Western blotting analyses were performed to assess levels of STAT5-pY694, STAT5, STAT3-pS727, STAT3, ERK1/2-pT202/Y204 and ERK1/2 upon overnight treatment of LAX7 cells with ruxolitinib (left) or of LAX7R cells with trametinib (right); n = 3 independent experiments. f, Patient-derived B-ALL cells (LAX7 and LAX7R) were treated with increasing concentrations of ruxolitinib or trametinib for 72 h. Relative viability (n = 3; mean ± s.d.) was measured. The x-axes indicate the concentrations of ruxolitinib or trametinib used. For gel source data, see Supplementary Fig. 1.

Source data