1. Supplemental Figure 1 Auranofin BSO Zn-BG ABC D carfilzomib

2. Supplemental Table1: Characteristics of CLL patients in this study; * status unknown

3. Supplemental Figure 2

4. CLL-7607 CLL-7620 Control 1.0  M AF, 24 h AB C Supplemental Figure 3 NLCCLL p=nsp=.005 -0.8 -0.6 -0.4 -0.2 0.0 0.2 R e l a t i v e c h a n g e i n v i a b i l i t y 1.0  M AF, 24 h 0 50 100 150 V i a b i l i t y ( % ) CLL, p=.005 NLC, p=ns 1.0  M AF Control

5. Before treatmentAfter treatment Mouse no. 16.96 x 10 6 1.31 x 10 6 Mouse no. 25.69x 10 6 9.00 x 10 5 Mouse no. 34.46 x 10 6 1.96 x 10 6 Mouse no. 48.73 x 10 6 2.32 x 10 6 Mouse no. 56.35 x 10 6 1.35 x 10 6 Leukemia cell burden Supplemental Table 2: Leukemia cell burden for individual TCL-1 mice pre- and post-treatment with 2 weeks of auranofin.

6. Affy_IDGeneFold Expression Change 203665_atHMOX159.076 203925_atGCLM46.992 225061_atDNAJA429.818 201841_s_atHSPB126.199 208864_s_atTXN18.697 36711_atMAFF16.865 211968_s_atHSP90AA111.342 203810_atDNAJB49.474 203693_s_atE2F36.613 201471_s_atSQSTM16.435 207574_s_atGADD45B5.875 217144_atUBB5.228 214359_s_atHSP90AB15.208 210519_s_atNQO15.098 204970_s_atMAFG5.00 225609_atGSR4.996 208680_atPRDX14.746 202284_s_atCDKN1A4.267 202417_atKEAP13.76 236213_atNFE2L23.585 200642_atSOD13.526 210176_atTLR13.171 236561_atTGFBR12.76 218284_atSMAD32.532 204194_atBACH12.332 243423_atTNIP12.324 206674_atFLT3-2.324 226068_atSYK-2.946 225973_atTAP2-2.579 226117_atTIFA-2.808 203508_atTNFRSF1B-2.583 38290_atRGS14-3.583 206341_atIL2RA-2.656 205698_s_atMAP2K6-4.603 214130_s_atPDE4DIP-3.992 214084_x_atNCF1C-3.134 214259_s_atAKR7A2-4.913 204279_atPSMB9-5.552 209040_s_atPSMB8-4.022 Supplemental Table 3: Gene expression changes of the 39 most up and downregulated genes in primary CLL cells following treatment with 1.0 µM of AF for 8 hours

7. Network ID Associated Network FunctionsScore 1 Protein Degradation, Protein Synthesis, Cellular Movement 41 2 Cellular Compromise, Cellular Function and Maintenance, Drug Metabolism 40 3 Free Radical Scavenging, Cellular Compromise, Molecular Transport 34 4 Endocrine System Disorders, Gastrointestinal Disease, Immunological Disease 29 5 Lipid Metabolism, Small Molecule Biochemistry, Infectious Disease 28 Supplemental Table 4: Ingenuity pathway analysis of the top 5 perturbed networks in Primary CLL cells treated with 1 µM of AF

8. Supplemental Figure 4

9. Zn-BG (µM) + AF (nM)FACI 10 + 1000.4550.726 10 + 1500.5290.933 15 + 1000.4240.775 15 + 1500.62150.765 20 + 1000.45750.722 20 + 1500.61550.775 MEC-1 A. Zn-BG (µM) + AF (nM) FACI 10 + 1000.4720.803 10 + 2500.6250.520 10 + 5000.8060.144 15 + 1000.5100.578 15 + 2500.6750.323 15 + 5000.8260.107 20 + 250.758.132 20 + 5000.8150.128 Primary CLL B. Supplemental Figure 5 C.D. BSO (µM) + AF (nM)FACI 1.0 + 100.07650.688 5.0 + 500.24350.443 7.5 + 750.63750.094 10 + 1000.8050.047 MEC-1 BSO (µM) + AF (nM)FACI 1.0 + 2500.580.547 2.0 + 2500.5580.761 3.0 + 2500.6500.463 4.0 + 2500.8200.201 5.0 + 2500.800.239 Primary CLL

10. Supplemental Figure 6 β-Actin CL. CASP3 MEC1 ---- +-+- -+-+ ++++ 2.5 mM NAC, 8 h 500 µM H 2 O 2, 8 h GRP78 Nrf2 CHOP A