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
HDAC1
Actin
2.0
1.5
1.0
0.5
Co-Treatment
Pre-Treatment
Syn
erg
y
Co
mb
ina
tio
n I
nd
ex
E.
40
30
20
10
5 10 15
RPMI+0.5%BSAHybridoma SFRPMI+10%FBS
CLL1 CLL2%
Su
bG
1 E
ve
nts
MutatedUnmutated
FLUVPA+FLU
60
40
20
%S
ub
G1
Ev
en
ts
N/S N/S
C.
40
30
20
10
Days5 10 15
Days
A.
80
60
40
20
%A
nn
exin
V P
osi
tivi
ty
VPA - - + +
FLU - + - +
B. D.
23-04-22
20
16
12
8
4
5
4
3
2
1
4 8 12 16 20 24
Time (HR)
Fold
Exp
ress
ion
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
C.
80
60
40
20% C
ells
with
D
iffus
e AO
sta
in
20
12
4
FL3
Geo
Mea
n
***
B.
D.
E.
%Sb
uG1
Even
ts
VehiclesCA074-Me
60
40
20
FLU - + - +
VPA - +
Acridine Orange
DAPI
Merge
FLU - + - +
VPA - +
Primary CLL
FLU - + - + - + - +
VPA - + - +
BJAB NALM-6
FLU - +
VPA - +
Primary CLL
Fo
ld i
nc
rea
se
in
H3
ac
ety
lati
on
Days
Figure S5
A.
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