Supplemental Table I. Design of Primers Used in Genotyping of 19 Candidate Gene Single

Supplemental table I. Design of primers used in genotyping of 19 candidate gene single nucleotide polymorphisms

Gene SNP ID PCR primer 1 PCR Primer 2 Extension Primer

ERCC1 rs3212961 ACGTTGGATGCTTGGAAGGGATTCAACAGC ACGTTGGATGAGGTGGATGTGGTAAGCAGG CATGGGCTGCTCCCTAGCCAGCCTCAC ERCC1 rs11615 ACGTTGGATGTTGATGGCTTCTGCCCTTCG ACGTTGGATGATAGTCGGGAATTACGTCGC GGGTCCAAATTCCCAGGGCAC ERCC2 rs238415 ACGTTGGATGTCGGCCTTGTGCTTCAATAG ACGTTGGATGGCAAAGGTGTCTTAAGTAGG GTTCAGTAGGACACAAAAGGCACCTG ERCC2 rs13181 ACGTTGGATGCACCAGGAACCGTTTATGGC ACGTTGGATGAGCAGCTAGAATCAGAGGAG GAATCAGAGGAGACGCTG ERCC2 rs1052555 ACGTTGGATGTCACAGATGCCAACCTCAAC ACGTTGGATGTCTGCCGCAGGAAGTACTTG CCCTGCCACCTGGACACCCTC ERCC4 rs1799802 ACGTTGGATGAAAAGGAACTGGTCCTAGAA ACGTTGGATGCTCTCCTTATTTTCTGCCTC ATAATTCAGTCAGTGCCTCCCACTTTG ERCC4 rs1800067 ACGTTGGATGCCGCTCCAAGAGTGATATAG ACGTTGGATGGGTCAAGTACTGATTTGTGC GATTTGTGCAAGTGATGACC ERCC5 rs4150388 ACGTTGGATGATGATTCTGAGAGGCAGGTC ACGTTGGATGGAGTCATCAAGCCTGAAAAG CCCCAGGCTTTCAGATTCTAAAC ERCC5 rs17655 ACGTTGGATGACCTGCCTCTCAGAATCATC ACGTTGGATGTTCGCAGCTGTTCTCCTTTG ATTAAAGATGAACTTTCAGCAT ERCC5 rs9514066 ACGTTGGATGCAGTTTCTGTTGCCATGGAG ACGTTGGATGTGTTATGCCTCTCTTCTGGG CCTCTCTTCTGGGTTTTTC ERCC5 rs9514067 ACGTTGGATGTAGAAGAGTCATCAAGCCTG ACGTTGGATGATGATTCTGAGAGGCAGGTC CCACAAATCCACCGCATGTATTCTTTC XRCC1 rs25487 ACGTTGGATGAGGATAAGGAGCAGGGTTGG ACGTTGGATGTAAGGAGTGGGTGCTGGACT CCCCTCGGCGGCTGCCCTCCC XRCC1 rs25489 ACGTTGGATGTTTGCCTGTCACTGCCCCCT ACGTTGGATGTTTGTCTTCTCCAGTGCCAG CCCTACAGTGCCAGCTCCAACTC XRCC2 rs3218536 ACGTTGGATGTTCTTCTGATGAGCTCGAGG ACGTTGGATGTCAGTGCTTAGAGAAGCTTG GAGAGAAGCTTGTAAATGACTATC XRCC4 rs2891980 ACGTTGGATGAGTCCTTGTGGAAGGTTTAG ACGTTGGATGGAAACTTGGGTGTTCTTAATG CCAATGAAATTATAGCCATTAGTTAC XRCC4 rs7734849 ACGTTGGATGACTCTTTGAACAACGAAGTG ACGTTGGATGACATACACAGATACACTGAC TTAGATACACTGACACAGATC XRCC4 rs1056503 ACGTTGGATGGCCTGATTCTTCACTACCTG ACGTTGGATGCTGCTGTTTCTCAGAGTTTC GAAGATGAGATGTGCTCCTTTTT XRCC4 rs963248 ACGTTGGATGGTACTGCCTCAAACTTCTGG ACGTTGGATGAAGCTGGGCATGATAGAGTG GGGCGGTTTAGGTTGGAGGATC XRCC5 rs1051685 ACGTTGGATGGCAAATGCTACTGCTTGCTC ACGTTGGATGCTTAACCCTTTCCAGAGTCC GGGGAATCCTCCAACAGCTGTCACA *Abbreviations: SNP, single nucleotide polymorphism; PCR, polymerase chain reaction;ERCC, excision repair cross complenting gene; XRCC, X-ray

repair cross complementing gene. Supplemental Table II. P-values of univariate analysis for imatinib treatment outcomes according to clinical variables

Referent Favorable MCR CCR MMR CMR LOR TF OS parameter parameter (n)

Age >50 ( 85) ≤50 (84) 0.730 0450 0.430 0.450 0.567 0.753 0.617

sex Male (96) Female (73) 0.345 0.830 0.301 0.466 0.099 0.312 0.269

Prior treatment Presence (35) Absence (134) 0.080 0.380 0.310 0.275 0.648 0.628 0.782

Allo-HSCT Done (7) Not done (161) 0.330 0.140 0.021 0.096 0.295 0.006 0.455

IM starting dose ＞400mg (3) ≤400 (165) 0.642 0.222 0.816 0.674 0.192 0.881 0.682

Exposure days of IM ≤1300adys(76) ＞1300days (90) 0.014 0.002 0.007 0.000 0.003 0.000 0.001

Add CG Presence (23) Absence (142) 0.866 0.572 0.882 0.859 0.444 0.228 0.680

Sokal score Low (48) Intermediate/High (93) 0.632 0.931 0.808 0.805 0.662 0.898 0.647

*Abbreviations: MCR, major cytogenetic response; CCR, complete cytogenetic response; MMR, major molecular response; CMR, complete molecular response

LOR, loss of response; TF, treatment failure; OS, overall survival; Allo-HSCT, allogeneic hematopoietic stem cell transplantation; IM, imatinib; Add CG additional cytogenetic abnormality Supplemental table III. P-values of univariate analysis for treatment outcomes according to the candidate genotypes in 169 chronic phase patients

Referent Favorable Gene SNP ID Call rate MCR CCR MMR CMR LOR TF OS genotype (n) genotype (n)

ERCC1 rs3212961 AA/CC (80) AC (78) 94.1% 0.136 0.389 0.382 0.950 0.992 0.550 0.218

ERCC1 rs11615 CC/CT (160) TT (9) 100% 0.026 0.032 0.172 0.776 0.184 0.866 0.053

ERCC2 rs238415 CC/CG (126) GG (41) 98.8% 0.152 0.211 0.061 0.182 0.237 0.151 0.345

ERCC2 rs13181 T(168) 99.4% ------

ERCC2 rs1052555 TC (14) CC (151) 97.6% 0.824 0.631 0.878 0.356 0.753 0.921 0.785

ERCC4 rs1799802 CC (169) 100% ------

ERCC4 rs1800067 GG (168) 99.4% ------

ERCC5 rs4150388 GG (168) 99.4% ------

ERCC5 rs17655 GG (48) CC/CG (69) 69.2% 0.128 0.026 0.070 0.211 0.312 0.074 0.296

ERCC5 rs9514066 CC (166) 98.2% ------

ERCC5 rs9514067 CC (169) 100% ------

XRCC1 rs25487 AA (7) AG/GG (161) 99.4% 0.514 0.271 0.715 0.857 0.328 0.006 0.567 XRCC1 rs25489 AA (4) AG/GG (164) 99.4% 0.475 0.952 0.869 0.752 0.026 0.488 0.541

XRCC2 rs3218536 GG (169) 100% ------

XRCC4 rs2891980 TT/TC (72) CC (93) 97.6% 0.569 0.847 0.769 0.338 0.326 0.338 0.898

XRCC4 rs7734849 AA/AT (146) TT (9) 91.7% 0.939 0.806 0.152 0.163 0.334 0.327 0.477

XRCC4 rs1056503 GT/GG (159) TT (9) 99.4% 0.890 0.801 0.144 0.169 0.317 0.303 0.443

XRCC4 rs963248 AG/GG (104) AA (10) 68.0% 0.274 0.494 0.040 0.138 0.365 0.105 0.463

XRCC5 rs1051685 AG (17) AA (150) 99.4% 0.172 0.407 0.940 0.631 0.611 0.746 0.481

*Abbreviations: SNP, single nucleotide polymorphism; ERCC, excision repair cross complementing gene; XRCC, X-ray repair cross complementing gene;

MCR, major cytogenetic response; CCR, complete cytogenetic response; MMR, major molecular response; CMR, complete molecular response; LOR, loss of response; TF, treatment failure; TFS, transformation free survival; OS, overall survival Supplemental table IV. Summary of internal validation using bootstrap survival analysis with ERCC1 (rs11615) and ERCC5 (rs17655).

Parameter Gene SNP ID Bootstrap p-value (95% C.I.) ERCC1 rs11615 0.020 (0.000, 0.822) MCR ERCC5 rs17655 0.162 (0.008, 0.9316) ERCC1 rs11615 0.030 (0.000, 0.812) CCR ERCC5 rs17655 0.040 (0.000, 0.662) ERCC1 rs11615 0.001 (0.000, 0.241) MMR ERCC5 rs17655 0.096 (0.001, 0.896) ERCC1 rs11615 0.548 (0.004,0.997) CMR ERCC5 rs17655 0.200 (0.002,0.939) ERCC1 rs11615 0.998 (0.998,0.999) LOR ERCC5 rs17655 0.296 (0.007,0.973) ERCC1 rs11615 0.997 (0.997,0.998) TF ERCC5 rs17655 0.062(0.000,0.858) ERCC1 rs11615 0.999 (0.998, 0.999) OS ERCC5 rs17655 0.32 (0.014, 0.996) *Abbreviations: MCR, major cytogenetic response; CCR, complete cytogenetic response; MMR, major molecular response; CMR, complete molecular response; LOR, loss of response; TF, treatment failure; OS, overall survival; ERCC, excision repair cross complementing gene; XRCC, X-ray repair cross complementing gene; SNP, single nucleotide polymorphisms; CI, confidence interval Supplemental table V. Results of multivariate analysis for treatment outcomes with clinical variable and significant genotypes

P-value MCR CCR MMR CMR LOR TF OS HR [95%C.I.] ERCC1 0.002 0.012 0.001 0.277 0.989 0.979 0.994

(rs11615) 5.14[1.83-14.43] 3.47[1.31-9.17] 5.71[2.13-15.30] 2.25 [0.52-9.75] 0[-] 0[-] 0[-] ERCC5 0.699 0.263 0.246 0.582 0.227 0.352 0.803

(rs17655) 1.10 [0.68-1.78] 1.35[0.80-2.28] 1.41[0.79-2.54] 1.20[0.63-2.26] 0.40[0.09-1.78] 0.67[0.29-1.55] 0.80[0.14-4.72] XRCC1 0.222 0.478 0.468 0.907 0.193 0.835 0.992

(rs25489) 0.52 [0.18-1.49] 0.65[0.20-2.15] 0.64[0.19-2.14] 0.92[0.21-4.04] 0.33[0.06-1.76] 0.86[0.20-3.70] 1.6E6[0.00-] Allo HSCT 0.789 0.343 0.395 0.595 0.993 0.051 0.93

(done vs not done) 0.82 [0.19-3.49] 0.38[0.05-2.83] 0.42[0.06-3.13] 0.57[0.07-4.53] 0[-] 3.51[0.99-12.40] 0.89[0.07-11.3] Exposure days of IM 0.006 0.015 0.243 0.026 0.062 0.000 0.004

(≤1300 vs >1300 days) 2.18 [1.25-3.80] 1.99[1.15-3.47] 1.43[0.79-2.60] 2.48[1.11-5.53] 0.21[0.04-1.08] 0.11[0.04-0.31] 0.04[0.00-0.35] Add CG abnormality 0.465 0.175 0.287 0.882 0.113 0.012 0.954

(presence vs absence) 0.32 [0.33-1.68] 0.53[0.21-1.33] 0.57[0.20-1.61] 0.92[0.31-2.77] 4.56[0.70-29.81] 3.46[1.31-9.10] 0.11[0.11-8.48] Sokal score 0.576 0.786 0.987 0.936 0.570 0.428 0.843

(low /Int. high) 1.15 [0.70-1.89] 1.07[0.64-1.80] 1.01[0.58-1.75] 0.98[0.53-1.80] 0.65[0.14-2.93] 0.72[0.31-1.64] 0.84[0.14-4.9] *Abbreviations: HR, hazard ratio; C.I., confidence interval; add GC abnormality, additional cytogenetic abnormality; Int, intermediate; ERCC, excision repair cross complementing gene; XRCC, X-ray repair cross complementing gene; MCR, major cytogenetic response; CCR, complete cytogenetic response;

MMR, major molecular response; CMR, complete molecular response; LOR, loss of response; TF, treatment failure; OS, overall survival

Supplemental figure I. Linkage disequilibrium plot of SNPs evaluated in the present study