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PatientVPA final dose (mg/kg/day) VPA final serum level (mM)(mg/L) 1500.62990.7 2451.081156.0 3200.57382.6 4700.765110.4 5200.61789.0 6300.54278 Supplemental.

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Presentation on theme: "PatientVPA final dose (mg/kg/day) VPA final serum level (mM)(mg/L) 1500.62990.7 2451.081156.0 3200.57382.6 4700.765110.4 5200.61789.0 6300.54278 Supplemental."— Presentation transcript:

1 PatientVPA final dose (mg/kg/day) VPA final serum level (mM)(mg/L) 1500.62990.7 2451.081156.0 3200.57382.6 4700.765110.4 5200.61789.0 6300.54278 Supplemental Table 1. Valproic Acid levels in the serum of treated CLL patients PatientVPA aloneVPA+FLUOverall Response pre-post-Cycle 1Cycle 2Cycle 3Cycle 4Cycle 5Cycle 6 CCM1-10.80.90.70.40.20.40.2O/S 1 SD CCM1-284.574.459.356.280.412.23.2O/S 3 SD CCM1-3112.1164.4O/S 2 PD CCM1-488.897.778.951.779.325.35.0O/S 3 SD CCM1-594.588.492.888.1124.337.319.023.9PR CCM1-698.1109.4106.036.923.411.54.98.1PD Supplemental Table 2. Absolute Lymphocyte values in treated CLL patient. O/S = Off Study, SD = Stable Disease, PR = Partial Response, PD = Progressive Disease 1. No further treatment required 2. Discontinued due to fatigue 3. Discontinued due to anemia

2 05/06/2016 BJABNALM-6I-83Cell Line -+-+-+Fludarabine (5 μM) -+--+--+--+--+--+-VPA ( 1 mM) --+--+--+--+--+--+Valpromide (1 mM) 15- 70- 15- 40- Figure S1 10- 100- H3 (K9K14-Ac) Histone 3 H4 (K5K8K12K16-Ac) Histone 4 HDAC1 Actin 2.0 1.5 1.0 0.5 Co- Treatment Pre- Treatment Synergy Combination Index E. 40 30 20 10 5 15 RPMI+0.5%BSA Hybridoma SF RPMI+10%FBS CLL1CLL2 %SubG1 Events Mutated Unmutated FLUVPA+ FLU 60 40 20 %SubG1 Events N/S C. 40 30 20 10 Days 51015 Days A. 80 60 40 20 %Annexin V Positivity VPA--++ FLU-+-+ B.D.

3 05/06/2016 20 16 12 8 4 5 4 3 2 1 48 162024 Time (HR) Fold Expression 4812162024 Time (HR) Fold Expression Vehicles Fludarabine (5 μM) VPA (1 mM) VPA + Fludarabine XIAPMcl-1 Figure S2 Day 1Day 2Time --++--++ VPA -+-+-+-+ FLU Mcl-1 XIAP GAPDH 8H16HTime --++--++ VPA -+-+-+-+ FLU Mcl-1 XIAP Tubulin A.B. C.D.

4 05/06/2016 15- -+VPA -+-+Fludarabine -+-+-+-+Chloroquine 40- < LC3 I < LC3 II Actin Figure S3

5 05/06/2016 FLU-+-+ VPA-+ Lyso Tracker DIC A. Figure S4 C. 80 60 40 20 % Cells with Diffuse AO stain 20 12 4 FL3 GeoMean ** * B. D. E. %SbuG1 Events Vehicles CA074-Me 60 40 20 FLU-+-+ VPA-+ Acridine Orange DAPI Merge FLU-+-+ VPA-+ Primary CLL FLU-+-+-+-+ VPA-+-+ BJABNALM-6 FLU-+ VPA-+ Primary CLL

6 Fold increase in H3 acetylation Days Figure S5 A.

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