1. Real-time RT-PCR : Real-time reverse-phase polymerase chain reaction
Supplemental Table 1. Details of handling and experimental usage of CLL lymphocytes obtained from patients
# of samples
 Assays and experimental details
Before oral duvelisib intake
(C1D1)
After 7 days of oral duvelisib intake
(C1D8)
After 28 days of oral duvelisib intake
(C2D1)
Sample
condition
Assays done 42
Frozen Blood
RNAseq
Nanostring 16
Fresh Blood 
Microfluidic chip real-time RT-PCR
Real-time RT-PCR
RPPA
Immunoblots
Microfluidic qRT-PCR (Applied Biosystems): included 93 apoptotic genes; 384 well plate
Real-time RT-PCR : Real-time reverse-phase polymerase chain reaction
RPPA: Reverse Phase Protein Array

2. Supplemental Table 2. Cytogenetics and prognostic markers of patient samples used for RPPA, immunoblot analyses.
Pt No
C1D1- WBC
C2D1- WBC
Rai Stage
Age
FISH
IGHV
ZAP70
CD38
Prior
therapy
#702
24.7
150.3 4 58
13q M
pos
neg 1
#877
5.8
17.6 72
11q
no PCR
#406
5.2
19.8 53
17p UM 5
#738
18.1
116.4 78
NA 
#733
35.9
15.2 3 61
 NA
#125
10.3
27.3 75 8
#005
25.9 69 2
#862
6.2
88.9 68
#431
73.3
82.6 71
T12
#087
60.9
76.9 56 7
#228
115.5
27.6 74
#345 13
16.9
#317
77.1 38
#524
55.3
120.4 80
#290 39
70.4 60
#310
54.3
118.4 82
NA: Information not available; PR: Partial response; SD: Stable disease; PROG: Progressive disease; M: Mutated; UM: Unmutated

3. Ligands, reagents, antibodies Source; Catalogue No
Supplemental Table 3. List of ligands, reagents and antibodies along with their sources
Ligands, reagents, antibodies
Source; Catalogue No
Navitoclax (ABT-737)
Provided by Abbott, Abbott Park, IL
Actin antibody (mouse)
Santa Cruz Biotechnology, Dallas, TX; sc-47778
Actin antibody (rabbit)
Cell Signaling Technology, Danvers, MA; 8457
Anti-IgM
MP Biomedicals, Santa Ana, CA; 55055
Bax antibody
Santa Cruz Biotechnology, Dallas, TX; sc-20067
Bax (Activated) antibody
Enzo Life Sciences, Farmingdale, NY; ALX C100
Bcl-2 antibody (mouse)
Dako, Carpinteria, CA; M0887
Bcl-2 antibody (rabbit)
Santa Cruz Biotechnology, Dallas, TX; sc-783
Bcl-xl antibody
Santa Cruz Biotechnology, Dallas, TX; ac-634
Bim antibody
Abcam, Cambridge, MA; ab32158
Dimethyl sulfoxide (DMSO)
Sigma Aldrich, St. Louis, MO
Duvelisib (IPI-145)
Infinity Pharmaceuticals, Inc. Cambridge, MA
Ibrutinib
Selleckchem, Houston, TX; S2680
Idelalisib
Gilead Sciences, Foster City, CA
Mcl-1 antibody
Life Technologies, Carlsbad, CA; AHO0102
Noxa antibody
Abcam, Cambridge, MA; ab13654
PARP antibody
BD Biosciences, San Jose, CA;
Puma antibody
Sigma Aldrich, St. Louis, MO; P4743
Recombinant Human IL-10
PeproTech, Rocky Hill, NJ;
Recombinant Human IL-2
PeproTech, Rocky Hill, NJ;
Recombinant Human sCD40-Ligand
PeproTech, Rocky Hill, NJ;
Vinculin antibody
Cell Signaling Technology, Danvers, MA; 13901
Venetoclax (ABT-199)
Xcessbio, San Diego, CA; M60075

4. Supplemental Table 4. Transcript and protein expressions of Bcl-2 family members measured through different techniques.
Bcl2 family
Gene Name
Protein Name
Mircofluidic chip qRTPCR
(Fold change)
RNA Seq
Nanostring
RPPA
Median
*P value n
Anti-apoptotic
BCL2
Bcl-2
2.81
0.002 5
1.40
< 31
1.38
0.0001 30
1.26
0.0012 16
BCL2A1 (BFL-1)
Bfl-1
0.92
0.527
1.25
0.0016 NA -
0.95
0.0112 9
BCL2L1 (BCL-XL)
Bcl-xL
0.60
0.683
0.55
0.0059
0.57
0.0004
0.97
0.5403
MCL1
Mcl-1
0.91
0.321
1.01
0.4059
0.93
0.0460
BCL2L2 (BCL-W)
Bcl-w
1.22
0.118
1.36
0.0008
BCL2L10 (BCL_B)
Bcl-b
0.69
0.602 ND --
0.98
0.9291
Pro-apoptotic multi-domain
BAK1
Bak
1.05
0.329
1.02
0.675
0.1581
BAX
Bax
1.20
0.308
0.4425
0.6952
0.89
0.0022
BOK
Bok
0.62
0.780
1.10
0.5379
Pro-apoptotic BH3 only
BAD
Bad
2.34
0.005
0.0227
1.08
0.5344
BBC3 (PUMA)
Puma
2.76
0.071
2.14
0.1203
1.24
0.0017
HRK
Hrk
20.08
0.012
3.11
<0.0001
2.56
PMAIP1 (NOXA)
Noxa
1.85
0.067
2.18
1.45
BCL2L11 (BIM)
Bim
1.31
0.459
1.37
1.34
BID
Bid
0.51
0.274
1.11
0.7408 1
0.6706
BIK
Bik
0.56
0.014
0.63
0.0104
0.38
BCL2L13 (BCL-RAMBO)
Bcl-rambo
1.58
0.029
1.13
0.0328
0.7918
BCL2L14 (BCL-G)
Bcl-g
1.07
0.863
BMF
Bmf
1.50
*Unpaired student t-test; ND, below limit of detection; NA, not applicable (not in the assay)

5. Patient Sample Duvelisib, nM + ABT-199, nM % Apoptosis Expected
Supplemental Table 5. Combination of duvelisib and venetoclax: Expected % apoptosis vs Observed % apoptosis . Red: Expected % apoptosis < Observed % apoptosis indicates either additive or synergistic combination. Green: Expected % apoptosis > Observed % apoptosis indicates either non-additive, non-synergistic or antagonistic combination. Method of calculating Expected % apoptosis: 1) Raw viability was normalized to "% viability”. 2) Expected % viability was calculated using following formula: “ % viability of drug A * % viability of drug B / 100” . 3) Expected % apoptosis was calculated as "100-(Expected % apoptosis)"
Patient
Sample
Duvelisib, nM +
ABT-199, nM
% Apoptosis
Expected
Observed
Culture condition
Suspension
IgM
Cytokine
#300
14.1
14.7
7.7
6.0
11.6
12.3
#576
5.9
6.5
7.5
8.5
2.0
2.4
21.3
26.8
14.9
13.1
15.5
6.1
12.7
9.4
14.3
2.2
#708
52.2
65.4
57.3
63.6
46.6
58.6
#215
20.7
23.6
6.4
14.4
10.3
18.9
#638
21.6
34.2
51.9
37.8
71.9
49.9
65.5
75.7
66.3
78.1
67.2
77.0
24.9
29.4
25.6
23.7
30.2
49.7
35.4
54.7
55.0
74.9
62.6