Supplementary table 1 Rai/ Binet IGHV Cytogenetic Relative viability Fludarabine- Sex Outcome CD38 (%) IGHV gene ZAP70 (%) Treatment (s) Stage identity (%) abnormalities* increase refractory 1 M 0/A Progressive 14,90 IGHV3-64*05 99,65 28,20 Del17p 18.0% 62,58322819 FCR n.a. 2 F 0/A Progressive 78,77 IGHV3-48*03 100,00 51,90 Del17p 24.8% 77,88052021 FCR n.a. 3 M 0/A Progressive 29,81 IGHV4-b*01 100,00 9,10 Del17p 12.0% 36,48 Len, Chl n.a. 4 M 1/A Stable 97,04 IGHV3-21*01 97,22 18,11 Normal 85,4191657 n.a. n.a. Chl+O, PCR, 5 F 0/A Progressive 87,00 IGHV4-39*07 100,00 43,20 Del13q 68.3% 35,23314039 n.a. HDMP+R 6 M 0/A Progressive 1,81 IGHV3-43*01 100,00 20,90 Del13q 77.7% 57,52490626 Chl n.a. Chl, FR, R-CHOP, 7 M 0/A Progressive 97,80 IGHV1-3*01 100,00 9,80 Del17p 88.5% 48,57389901 n.a. HDMP+R 8 F 2/B Progressive 69,07 IGHV5-a*03 100,00 16,50 Del17p 77.2% 107,9656878 FCR, BA No R-CHOP, FCR, 9 M 1/A Progressive 2,13 IGHV3-23*01 97,22 29,80 Del11q 16.3% 134,5866919 Yes Flavopiridol, BA 10 M 2/A Progressive 0,36 IGHV3-30*02 92,01 0,38 Del13q 81.9% 78,91844953 Unknown n.a. 11 M 2/B Progressive 15,17 IGHV3-20*01 100,00 13,20 Del11q 95.3% 75,52880995 FCR, R-CHOP, BR No 12 M 0/A Stable 0,14 IGHV3-30*02 90,62 7,40 Del13q 13.0% 13,0939004 n.a. n.a. 13 M 1/A Stable 0,18 IGHV3-53*01 91,23 9,50 Del13q 82.8% 18,10905751 n.a. n.a. 14 F 0/A Stable 4,00 IGHV3-9*01 96,50 47,70 Normal 18,56573723 n.a. n.a. 15 F 0/A Stable 71,76 IGHV1-24*01 100,00 69,80 n.d. 76,35699267 n.a. n.a. 16 M 0/A Progressive 91,64 IGHV3-7*01 99,65 0,70 Del17p 16.1% 269,5968555 BR N.A. 17 M 2/A Stable 92,00 IGHV1-2*04 100,00 25,00 Trisomy 12 77.1% 103,3478272 n.a. n.a. 18 M 1/A Progressive 7,43 IGHV4-61*02 93,66 10,71 Del13q 73.5% 37,2238619 n.a. n.a. 19 M 0/A Stable 9,73 n.d. 100,00 83,80 Normal 76,35699267 n.a. n.a. 20 M 2/B Progressive 74,90 IGHV1-69*06 100,00 n.d. 47,94100564 R-CHOP N.A. 21 F nd/nd Progressive IGHV3-7*03 99,65 Del17p 21.0% 78,10188375 FCR Yes 22 F 0/A Progressive 10,00 IGHV3-74*01 100,00 38,20 Del11q 30.6% 108,3321673 Chl+O N.A. 23 F n.d./A Stable IGHV3-23*01 88,19 n.d. 53,25774997 n.a. n.a. 24 F n.d./n.d. Progressive 0,09 IGHV3-66*02 96,14 Del17p 20.0% 97,94587461 Chl N.A. 25 F 0/A Stable 5,82 n.d. 24,00 Del13q 84.0% 26,90749111 n.a. n.a. 26 M 0/A Stable 32,70 IGHV1-69*01 100,00 35,01 n.d. 103,0650103 n.a. n.a. 27 M 0/A Stable 11,00 IGHV3-48*03 100,00 46,50 Del11q 75.2% 87,49194965 n.a. n.a. 28 F 1/B Stable 80,64 35,41 Trisomy 12 48.5% 36,29335159 n.a. n.a. 29 F 0/A Stable 0,17 IGHV3-30*01 92,71 87,21 Del13q 60.0% 123,099052 n.a. n.a. 30 M 0/A Stable 0,50 o.f. o.f. 25,40 Del17p 16.2% -2,585090833 n.a. n.a. 31 M 0/A Stable 4,30 o.f. o.f. 10,00 Del13q 12.4% 2,479668616 n.a. n.a. 32 F 0/A Progressive 1,20 IGHV3-23*01 98,26 25,7 Del13q 82.0% -2,044761256 FCR, Len No 33 M n.d./A Stable 0,68 IGHV3-23*01 91,99 17,7 Del13q 12.0% -20,46049377 n.a. n.a. 34 F 0/A Stable 0,04 IGHV3-23*01 88,54 3,70 Del13q 89.3% -20,99170888 n.a. n.a. 35 M 0/A Stable 0,33 IGHV5-51*03 93,40 3,25 Del13q 26.7% -20,11220306 n.a. n.a. 36 F 0/A Stable 0,96 IGHV4-30-4*01 92,78 13,80 Normal -2,362618533 n.a. n.a. 37 F 0/A Stable 0,12 IGHV1-3*01 88,19 7,80 Del13q 94.9% 9,460511294 n.a. n.a. 38 M 0/A Stable 0,22 IGHV4-4*02 100,00 33,40 Del13q 14.5% 3,939179956 n.a. n.a. 39 F 0/A Stable 0,00 IGHV3-23*01 89,24 0,20 Del13q 16.3% -9,900894266 n.a. n.a. 40 M 1/A progressive 11,55 IGHV3-30*03 100,00 0,30 n.d. 6,358412429 n.a. n.a. 41 M 0/A progressive 1,31 IGHV4-34*01 95,44 16,50 Del17p 97.7% 7,983980104 FC, A, Flavopiridol Yes 42 M 0/A Stable 0,24 IGHV3-23*01 92,71 25,35 Normal -15,13362971 n.a. n.a. 43 M 0/A Stable 0,00 IGHV4-34*01 95,05 n.d. 8,917831145 n.a. n.a. 44 F 0/A Stable 0,06 IGHV3-48*03 89,24 1,90 Del13q 74.5% -20,45124992 n.a. n.a. Table 1. Clinical and biological features of the patients analyzed. * according to Dohner’s hierarchical classification; n.d. indicates not done; o.f. indicates out of frame; n.a. not applicable FCR fludarabine, cyclophosphamide, rituximab; Len lenalidomide; Chl chlorambucil; O ofatumumab; PCR pentostatine, cyclophosphamide, rituximab; HDMP high-dose methylprednisolone; BA bendamustine, alemtuzumab; BR bendamustine, rituximab;Supplementary R-CHOP rituximab, table 2 cyclophosphamide, doxorubicin, vincristine, prednisone; Relative viability increase ∆ viability % (CpG-CNTRL) 3μM of Fludarabine. Supplementary table 2 Symbol Description Gname 1 ABL1 C-abl oncogene 1, receptor tyrosine kinase ABL/JTK7/bcr/abl/c-ABL/p150/v-abl 2 AKT1 V-akt murine thymoma viral oncogene homolog 1 AKT/PKB/PKB-ALPHA/PRKBA/RAC/RAC-ALPHA 3 APAF1 Apoptotic peptidase activating factor 1 APAF-1/CED4 4 BAD BCL2-associated agonist of cell death BBC2/BCL2L8 5 BAG1 BCL2-associated athanogene RAP46 6 BAG3 BCL2-associated athanogene 3 BAG-3/BIS/CAIR-1/MGC104307 7 BAG4 BCL2-associated athanogene 4 BAG-4/SODD 8 BAK1 BCL2-antagonist/killer 1 BAK/BAK-LIKE/BCL2L7/CDN1/MGC117255/MGC3887 9 BAX BCL2-associated X protein BCL2L4 10 BCL10 B-cell CLL/lymphoma 10 CARMEN/CIPER/CLAP/c-E10/mE10 11 BCL2 B-cell CLL/lymphoma 2 Bcl-2 12 BCL2A1 BCL2-related protein A1 ACC-1/ACC-2/BCL2L5/BFL1/GRS/HBPA1 13 BCL2L1 BCL2-like 1 BCL-XL/S/BCL2L/BCLX/Bcl-X/DKFZp781P2092/bcl-xL/bcl-xS 14 BCL2L10 BCL2-like 10 (apoptosis facilitator) BCL-B/Boo/Diva/MGC129810/MGC129811 15 BCL2L11 BCL2-like 11 (apoptosis facilitator) BAM/BIM/BIM-alpha6/BIM-beta6/BIM-beta7/BOD/BimEL/BimL 16 BCL2L2 BCL2-like 2 BCL-W/BCLW/KIAA0271 17 BCLAF1 BCL2-associated transcription factor 1 BTF/KIAA0164/bK211L9.1 18 BFAR Bifunctional apoptosis regulator BAR/RNF47 19 BID BH3 interacting domain death agonist FP497/MGC15319/MGC42355 20 BIK BCL2-interacting killer (apoptosis-inducing) BIP1/BP4/NBK 21 NAIP NLR family, apoptosis inhibitory protein BIRC1/FLJ18088/FLJ42520/FLJ58811/NLRB1/psiNAIP 22 BIRC2 Baculoviral IAP repeat-containing 2 API1/HIAP2/Hiap-2/MIHB/RNF48/cIAP1 23 BIRC3 Baculoviral IAP repeat-containing 3 AIP1/API2/CIAP2/HAIP1/HIAP1/MALT2/MIHC/RNF49 24 XIAP X-linked inhibitor of apoptosis API3/BIRC4/ILP1/MIHA/XLP2 25 BIRC6 Baculoviral IAP repeat-containing 6 APOLLON/BRUCE/FLJ13726/FLJ13786/KIAA1289 26 BIRC8 Baculoviral IAP repeat-containing 8 ILP-2/ILP2/hILP2 27 BNIP1 BCL2/adenovirus E1B 19kDa interacting protein 1 NIP1/SEC20/TRG-8 28 BNIP2 BCL2/adenovirus E1B 19kDa interacting protein 2 BNIP-2/NIP2 29 BNIP3 BCL2/adenovirus E1B 19kDa interacting protein 3 NIP3 30 BNIP3L BCL2/adenovirus E1B 19kDa interacting protein 3-like BNIP3a/NIX 31 BRAF V-raf murine sarcoma viral oncogene homolog B1 B-RAF1/BRAF1/FLJ95109/MGC126806/MGC138284/RAFB1 32 NOD1 Nucleotide-binding oligomerization domain containing 1 CARD4/CLR7.1/NLRC1 33 CARD6 Caspase recruitment domain family, member 6 CINCIN1 34 CARD8 Caspase recruitment domain family, member 8 CARDINAL/DACAR/Dakar/NDPP/NDPP1/TUCAN 35 CASP1 Caspase 1, apoptosis-related cysteine peptidase ICE/IL1BC/P45 36 CASP10 Caspase 10, apoptosis-related cysteine peptidase ALPS2/FLICE2/MCH4 37 CASP14 Caspase 14, apoptosis-related cysteine peptidase MGC119078/MGC119079 38 CASP2 Caspase 2, apoptosis-related cysteine peptidase CASP-2/ICH-1L/ICH-1L/1S/ICH1/NEDD2 39 CASP3 Caspase 3, apoptosis-related cysteine peptidase CPP32/CPP32B/SCA-1 40 CASP4 Caspase 4, apoptosis-related cysteine peptidase ICE(rel)II/ICEREL-II/ICH-2/Mih1/TX/TX 41 CASP5 Caspase 5, apoptosis-related cysteine peptidase ICE(rel)III/ICEREL- III/ICH-3/MGC141966 42 CASP6 Caspase 6, apoptosis-related cysteine peptidase MCH2 43 CASP7 Caspase 7, apoptosis-related cysteine peptidase CMH-1/ICE-LAP3/MCH3 44 CASP8 Caspase 8, apoptosis-related cysteine peptidase ALPS2B/CAP4/Casp-8/FLICE/MACH/MCH5/ 45 CASP9 Caspase 9, apoptosis-related cysteine peptidase APAF-3/APAF3/CASPASE-9c/ICE-LAP6/MCH6 46 CD40 CD40 molecule, TNF receptor superfamily member 5 Bp50/CDW40/MGC9013/TNFRSF5/p50 47 CD40LG CD40 ligand CD154/CD40L/HIGM1/IMD3/T-BAM/TNFSF5/TRAP/gp39 48 CFLAR CASP8 and FADD-like apoptosis regulator CASH/CASP8AP1/CLARP/FLAME/I-FLICE/MRIT/c-FLIP 49 CIDEA Cell death-inducing DFFA-like effector a CIDE-A 50 CIDEB Cell death-inducing DFFA-like effector b - 51 CRADD CASP2 and RIPK1 domain containing adaptor w ith death domain MGC9163/RAIDD 52 DAPK1 Death-associated protein kinase 1 DAPK/DKFZp781I035 53 DFFA DNA fragmentation factor, 45kDa, alpha polypeptide DFF-45/DFF1/ICAD 54 FADD Fas (TNFRSF6)-associated via death domain GIG3/MGC8528/MORT1 55 FAS Fas (TNF receptor superfamily, member 6) ALPS1A/APO-1/APT1/CD95/FAS1/FASTM/TNFRSF6 56 FASLG Fas ligand (TNF superfamily, member 6) APT1LG1/CD178/CD95L/FASL/TNFSF6 57 GADD45A Grow th arrest and DNA-damage-inducible, alpha DDIT1/GADD45 58 HRK Harakiri, BCL2 interacting protein (contains only BH3 domain) DP5/HARAKIRI 59 IGF1R Insulin-like grow th factor 1 receptor CD221/IGFIR/IGFR/JTK13 60 LTA Lymphotoxin alpha (TNF superfamily, member 1) LT/TNFB/TNFSF1 Symbol Description Gname 61 LTBR Lymphotoxin beta receptor (TNFR superfamily, member 3) CD18/LT-BETA-R/TNF-R-III/TNFCR/TNFR2-RP/TNFRSF3 62 MCL1 Myeloid cell leukemia sequence 1 (BCL2-related) BCL2L3/EAT/MCL1L/MCL1S/Mcl-1/TM 63 NOL3 Nucleolar protein 3 (apoptosis repressor w ith CARD domain) ARC/CARD2/MYC/MYP/NOP/NOP30 64 PYCARD PYD and CARD domain containing ASC/CARD5/MGC10332/TMS/TMS-1/TMS1 65 RIPK2 Receptor-interacting serine-threonine kinase 2 CARD3/CARDIAK/CCK/GIG30/RICK/RIP2 66 TNF Tumor necrosis factor (TNF superfamily, member 2) DIF/TNF-alpha/TNFA/TNFSF2 67 TNFRSF10A Tumor necrosis factor receptor superfamily, member 10a APO2/CD261/DR4/MGC9365/TRAILR-1/TRAILR1 68 TNFRSF10B Tumor necrosis factor receptor superfamily, member 10b CD262/DR5/KILLER/KILLER/DR5/TRAIL-R2/TRAILR2/TRICK2 69 TNFRSF11B Tumor