Table 1.
Summary of studies of the efficacy of IM treatment in relation to pharmacokinetic genetic variants*
| Genes | SNP* | Base substitution† | Functional effect‡ | No of patients | Response criteria | IM dosage | Association | References |
|---|---|---|---|---|---|---|---|---|
| ABCB1 | rs1128503 | C1236T | + | 90 French | MMR at 12 months | 400 mg in front line or 2nd line after IFN | Higher MMR with 1236T allele | [20] |
| - | 62 Japanese | MMR | ≥400 and ≤300 mg | No | [26] | |||
| 229 Canadian | CyR and MR at 1, 1.5, 2, 3, 4 and 5 years§ | 400, 600 or 800 mg | No | [25] | ||||
| 87 English | MMR¶ at 18 months | 400 mg | No | [24] | ||||
| 46 Dutch | Cumulative incidence of MMR and CMR at 12 months | 800 mg | Higher MMR and CMR with CC genotype | [22] | ||||
| 557 French | MMR at 12 months | 400 mg; 400 mg + IFN 400 mg + AraC; 600 mg | No | [21] | ||||
| 52 Chinese | CCyR at 12 months | 400 mg | Lower CCyR with TT genotype | [23] | ||||
| rs2032582 | G2677T/A | + | 90 French | MMR at 12 months | 400 mg in front line or 2nd line after IFN | Lower MMR with 2677G allele | [20] | |
| - | 62 Japanese | MMR | ≥400 and ≤300 mg | No | [26] | |||
| 229 Canadian | CyR and MR at 1, 1.5, 2, 3, 4 and 5 years§ | 400, 600 or 800 mg | No | [25] | ||||
| 46 Dutch | Cumulative incidence of MMR and CMR at 12 months | 800 mg | Lower CMR with TT genotype | [22] | ||||
| 557 French | MMR at 12 months | 400 mg; 400 mg + IFN 400 mg + AraC; 600 mg | Higher MMR with 2677G allele in the arm 400 mg + AraC | [21] | ||||
| 52 Chinese | CCyR at 12 months | 400 mg | Higher CCyR with AG/AT/AA genotypes | [23] | ||||
| rs1045642 | C3435T¥ | - | 90 French | MMR at 12 months | 400 mg in front line or 2nd line after IFN | No | [20] | |
| - | 62 Japanese | MMR | ≥400 and ≤300 mg | No | [26] | |||
| ABCB1 | rs1045642 | C3435T¥ | 229 Canadian | CyR and MR at 1, 1.5, 2, 3, 4 and 5 years§ | 400, 600 or 800 mg | Overall survival lower with TT genotype but not confirmed in multivariate analysis | [25] | |
| 46 Dutch | Cumulative incidence of MMR and CMR at 12 months | 800 mg | Lower CMR with TT genotype | [22] | ||||
| 557 French | MMR at 12 months | 400 mg; 400 mg + IFN 400 mg + AraC; 600 mg | No | [21] | ||||
| 52 Chinese | CCyR at 12 months | 400 mg | Higher CCyR with CC genotype | [23] | ||||
| ABCG2 | rs717620 | - | 62 Japanese | MMR | ≥400 and ≤300 mg | No | [26] | |
| rs2231142 | C421A¥ | + | 62 Japanese | MMR | ≥400 and ≤300 mg | No | [26] | |
| 229 Canadian | CyR and MR at 1, 1.5, 2, 3, 4 and 5 years§ | 400, 600 or 800 mg | Higher CMR with AA genotype; more frequent need for IM dose escalation for CC genotype | [25] | ||||
| rs2231137 | G34A | 229 Canadian | CyR and MR at 1, 1.5, 2, 3, 4 and 5 years§ | 400, 600 or 800 mg | Lower MCyR and CCyR with GG genotypes | [25] | ||
| SLC22A1 | rs12208357 | 32 Austrian | MMR at 18 months | 400 mg | No | [52] | ||
| - | 132 English | MMR | 400 mg | No | [37] | |||
| 229 Canadian | CyR and MR at 1, 1.5, 2, 3, 4 and 5 years§ | 400, 600 or 800 mg | No | [25] | ||||
| - | 136 Australian | MMR at 2 years | < 600 mg or ≥600 mg | No | [38] | |||
| rs2282143 | - | 132 English | MMR | 400 mg | No | [37] | ||
| - | 62 Japanese | MMR | ≥400 and ≤300 mg | No | [26] | |||
| 229 Canadian | CyR and MR at 1, 1.5, 2, 3, 4 and 5 years§ | 400, 600 or 800 mg | No | [25] | ||||
| rs34130495 | G1201A¥ | - | 132 English | MMR | 400 mg | Higher MMR with GA genotypes | [37] | |
| SLC22A1 | - | 136 Australian | MMR at 2 years | < 600 mg or ≥600 mg | No | [38] | ||
| rs622342 | - | 132 English | MMR | 400 mg | No | [37] | ||
| rs1867351 | - | 62 Japanese | MMR | ≥400 and ≤300 mg | No | [26] | ||
| 229 Canadian | CyR and MR at 1, 1.5, 2, 3, 4 and 5 years§ | 400, 600 or 800 mg | No | [25] | ||||
| rs683369 | C480G | - | 62 Japanese | MMR | ≥400 and ≤300 mg | No | [26] | |
| 229 Canadian | CyR and MR at 1, 1.5, 2, 3, 4 and 5 years§ | 400, 600 or 800 mg | Higher risk of loss of response and treatment failure with GG genotypes | [25] | ||||
| rs628031 | A1222G | - | 62 Japanese | MMR | ≥400 and ≤300 mg | Higher MMR with GG genotypes | [26] | |
| 229 Canadian | CyR and MR at 1, 1.5, 2, 3, 4 and 5 years§ | 400, 600 or 800 mg | No | [25] | ||||
| - | 136 Australian | MMR at 2 years | < 600 mg or ≥600 mg | No | [38] | |||
| rs 72552763 | - | 136 Australian | MMR at 2 years | < 600 mg or ≥600 mg | No | [38] | ||
| SLCO1B3 | rs4149117 | - | 62 Japanese | MMR | ≥400 and ≤300 mg | No | [26] | |
| CYP3A5 | rs776746 | A6986G | - | 62 Japanese | MMR | ≥400 and ≤300 mg | No | [26] |
| 229 Canadian | CyR and MR at 1, 1.5, 2, 3, 4 and 5 years§ | 400, 600 or 800 mg | Lower MCyR and CCyR with AA genotypes | [25] | ||||
| 265 Indian | Hematological response (HR) | 400 mg | Lower HR with GG genotypes | [41] | ||||
| rs28383468 | 229 Canadian | CyR and MR at 1, 1.5, 2, 3, 4 and 5 years§ | 400, 600 or 800 mg | No | [25] | |||
| AGP | rs3182041 | 229 Canadian | CyR and MR at 1, 1.5, 2, 3, 4 and 5 years§ | 400, 600 or 800 mg | No | [25] |
*All patients were in chronic phase except for the study of Kim et al. [25], in which 203 patients were in chronic phase and 26 patients in accelerated phase or in blast crisis. †The base substitution and rs number taken from the National Centre for Biotechnology information SNP database [53] are indicated for polymorphisms positively associated with IM response. For the remaining SNPs for which no association was found, only the rs number is indicated. ‡Functional impact in vivo: association had been found between polymorphisms and transcript levels of candidate genes or with trough IM concentration. §CyR, cytogenetic response; MR, molecular response; the cumulative incidence of major cytogenetic response (MCyR), CCyR, MMR, complete molecular response (CMR), loss of response, treatment failure and overall survival was measured. ¶MMR in patients with CCyR. ¥Polymorphisms with demonstrated functional effect in vitro.