Patient VPA final dose (mg/kg/day)

VPA final serum level(mM) (mg/L)

1 50 0.629 90.72 45 1.081 156.03 20 0.573 82.64 70 0.765 110.45 20 0.617 89.06 30 0.542 78

Supplemental Table 1. Valproic Acid levels in the serum of treated CLL patients

Patient VPA alone VPA+FLU Overall Responsepre- post- Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6

CCM1-1 0.8 0.9 0.7 0.4 0.2 0.4 0.2 O/S1 SDCCM1-2 84.5 74.4 59.3 56.2 80.4 12.2 3.2 O/S3 SDCCM1-3 112.1 164.4 O/S2 PDCCM1-4 88.8 97.7 78.9 51.7 79.3 25.3 5.0 O/S3 SDCCM1-5 94.5 88.4 92.8 88.1 124.3 37.3 19.0 23.9 PRCCM1-6 98.1 109.4 106.0 36.9 23.4 11.5 4.9 8.1 PD

Supplemental Table 2. Absolute Lymphocyte values in treated CLL patient.

O/S = Off Study, SD = Stable Disease, PR = Partial Response, PD = Progressive Disease1. No further treatment required2. Discontinued due to fatigue3. Discontinued due to anemia

23-04-22

BJAB NALM-6 I-83 Cell Line

- + - + - + Fludarabine (5 μM)

- + - - + - - + - - + - - + - - + - VPA ( 1 mM)

- - + - - + - - + - - + - - + - - + Valpromide (1 mM)15-

15-

70-

15-

40-

Figure S1

10-

100-H3 (K9K14-Ac)

Histone 3

H4 (K5K8K12K16-Ac)

Histone 4

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1.5

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RPMI+0.5%BSAHybridoma SFRPMI+10%FBS

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Days

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23-04-22

20

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4

3

2

1

4 8 12 16 20 24

Time (HR)

Fold

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4 8 12 16 20 24

Time (HR)

Fold

Exp

ress

ion Vehicles

Fludarabine (5 μM)VPA (1 mM)VPA + Fludarabine

XIAP Mcl-1

Figure S2

Day 1 Day 2 Time

- - + + - - + + VPA

- + - + - + - + FLU

Mcl-1

XIAP

GAPDH

8H 16H Time

- - + + - - + + VPA

- + - + - + - + FLU

Mcl-1

XIAP

Tubulin

A. B.

C. D.

23-04-22

15-

- + VPA

- + - + Fludarabine

- + - + - + - + Chloroquine

40-

< LC3 I< LC3 II

Actin

Figure S3

23-04-22

FLU - + - +

VPA - +

LysoTracker

DIC

A.

Figure S4

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FLU - + - +

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Acridine Orange

DAPI

Merge

FLU - + - +

VPA - +

Primary CLL

FLU - + - + - + - +

VPA - + - +

BJAB NALM-6

FLU - +

VPA - +

Primary CLL

Fo

ld i

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Figure S5

A.