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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PatientVPA final dose (mg/kg/day) VPA final serum level (mM)(mg/L) 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 CCM O/S 1 SD CCM O/S 3 SD CCM O/S 2 PD CCM O/S 3 SD CCM PR CCM PD 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

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

05/06/ Time (HR) Fold Expression 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.

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

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

Fold increase in H3 acetylation Days Figure S5 A.