Genetic variants in ABCB1 and ABCG2 raise imatinib trough levels in CML patients

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Expert review of anticancer therapy Published May 4, 2026 Medically reviewed May 8, 2026 Study authors: de Moraes Francisco Cezar Aquino, Matheus Gustavo Tadeu Freitas Uchôa, Rego Luis Henrique Rios Morei… PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

ABCB1 and ABCG2 variants significantly increase imatinib trough levels, supporting pharmacogenetic screening for CML therapy optimization.

A systematic review and meta-analysis of 1,098 heterozygous patients, 519 variant carriers, and 896 wild-type individuals examined genetic polymorphisms in drug transporter genes ABCB1 and ABCG2 among patients with chronic myeloid leukemia treated with imatinib. The primary outcome was imatinib plasma trough concentrations (Ctrough), with wild-type individuals and other genotypes serving as comparators.

Key findings indicated that the ABCB1 c.3435C>T TT genotype was associated with significantly higher Ctrough compared to the CC genotype, with a mean difference of 299.84 (95% CI: 208.06-391.62; p = 0.0097). Similarly, the ABCB1 c.2677G>T GT and TT genotypes showed higher levels versus GG, with mean differences of 327.62 and 289.22, respectively, both with low p-values.

Additionally, the ABCG2 c.412C>A CA carriers exhibited increased Ctrough compared to CC, with a mean difference of 186.83 (95% CI: 67.11-306.56; p = 0.022). These results consistently demonstrated higher drug exposure in variant carriers across multiple polymorphisms.

The analysis supports the role of pharmacogenetic screening in optimizing imatinib therapy, potentially improving efficacy and reducing adverse outcomes. Limitations include unreported settings and follow-up, but the robust effect sizes and statistical significance underscore the clinical relevance of these genetic markers.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

PMID41367289

View Original Abstract ↓

INTRODUCTION: Chronic myeloid leukemia (CML) is effectively treated with tyrosine kinase inhibitors such as imatinib, though drug response varies among patients. Genetic polymorphisms in drug transporter genes ABCB1 and ABCG2 influence imatinib plasma trough concentrations (Ctrough). METHODS: Statistical analyses were performed using fixed-effect models and heterogeneity was assessed using I² statistic. RESULTS: This meta-analysis evaluated nine studies including 1,098 heterozygous patients, 519 variant carriers, and 896 wild-type individuals. Results showed significantly higher Ctrough in patients with the ABCB1 c.3435C>T TT genotype compared with CC with data of 7 studies (MD = 299.84; 95% CI: 208.06-391.62; = 0.0097; I² = 77%). Similarly, ABCB1 c.2677G>T GT (MD = 327.62; 95% CI: 198.90-456.34; = 0.0008; I² = 52%) and TT (MD = 289.22; 95% CI: 135.63-442.81; < 0.001; I² = 12%) genotypes were associated with higher levels than GG, both assessed by 4 studies. Additionally, data from 5 studies observed that ABCG2 c.412C>A CA carriers had increased Ctrough versus CC (MD = 186.83; 95% CI: 67.11-306.56; = 0.022; I² = 32%). CONCLUSIONS: These findings support the role of pharmacogenetic screening in optimizing imatinib therapy, improving efficacy, and reducing risks of adverse outcomes. REGISTRATION: PROSPERO (CRD42024574179).