Supplementary Table 1. Defining CIP2A status The table below shows the diagnostic CIP2A level (as mean fluorescence intensity; MFI)for all 74 patients.The range was 0-52, the interquartile range was 0.48 – 8.65, the median was 2.85 and the mean was 6.5. High CIP2A patients are defined as those patients with a CIP2A level greater than or equal to 7.3. The cut-off value was derived using ROC curve analysis for the prediction of BC based on the diagnostic CIP2A protein level; minimisation of the Euclidian distance between the ROC curve and the corner (0, 1) was the criterion used. The optimal cut-off value produced an AUCROC = 0.902 (95% CI: 0.832, 0.973). Patient First line treatment CIP2A Status CIP2A (MFI) 1 imatinib Low 0.0 2 3 4 5 6 7 8 9 10 11 12 13 0.3 14 0.4 15 0.7 16 0.9 17 18 1.2 19 1.3 20 1.6 21 low 1.7 22 2.0 23 24 2.2 25 2.8 26 3.7 27 4.5 28 4.9 29 5.0 30 5.7 31 6.1 32 6.2 33 6.3 34 high 7.3 35 9.1 36 9.9 37 12.9 38 15.0 39 16.4 40 18.0 41 19.7 42 25.9 43 26.3 44 35.3 45 2G TKI 46 47 48 49 50 51 52 53 54 55 2.5 56 2.6 57 2.9 58 3.0 59 3.5 60 61 4.0 62 63 5.5 64 6.7 65 7.2 66 67 19.0 68 10.1 69 10.7 70 11.5 71 13.6 72 17.0 73 18.3 74 52.0   Average 6.4

Supplementary Figure 1. Assessment of PP2A activity in K562 cells. PP2A activity was assessed by two methods, the PP2A phosphatase immunoprecipitation activity assay and PP2A Y307 inactive protein level by flow cytometry. On PP2A activation either by FTY720 or imatinib, both activity increases and PP2A Y307 decreases (panels A and B). On PP2A inhibition by okadaic acid, the opposite is seen (panels C and D). A B Isotype control Untreated 5µM Imatinib 2.5µM FTY720 C D Isotype Control Untreated 6nM okadaic acid

Supplementary Figure 2. Viability post TKI treatment CML patient cells were incubated with 5μM imatinib, 150nM dasatinib and 5μM nilotinib for 24 hours. Viability was assessed by propidium iodide staining (PI)n=10. p=0.02 p=0.05 p=0.02

Supplementary Figure 3. siRNA mediated inhibition of the CIP2A/c-Myc/E2F1 pathway in K562 cells K562 cells were treated with CIP2A siRNA Panels A-C, c-Myc siRNA Panels D-F and E2F1 siRNA Panels G-I (n=4) for 72 hours. A B C CIP2A siRNA p=0.009 p=0.004 p=0.002 D E F c-Myc siRNA p=0.03 p=0.003 p=0.003 G H I E2F1 siRNA p=0.003 p=0.004