Meta‐Analysis of Imatinib Resistance in Chronic Myeloid Leukemia due to BIM Gene Deletion and Single Nucleotide Polymorphisms Reveals Ethnic Variations in Prevalence
Abhinav Bhattarai, Dimitri Kountouris, Sanjit Sah, Rachana Mehta, Ranjit SahABSTRACT
Background and Aim
Deletion and single nucleotide polymorphisms in the BIM gene have been proposed as a potential contributor of intrinsic resistance to imatinib in patients with chronic myeloid leukemia (CML). Individual studies, particularly in East Asian population, have reported higher frequency of these gene variants and have suggested higher resistance rates, however, results remain varied across other non‐East Asian cohorts. We aimed to determine the pooled prevalence of BIM deletion and polymorphisms across East Asian and non‐East Asian populations and to evaluate their pooled association with imatinib resistance in CML.
Methods
A meta‐analysis was performed using R Studio 2024.12.0. PubMed, Embase, and Scopus were searched through October 2025. Studies reporting BIM deletion or polymorphisms and imatinib treatment response outcomes in CML patients were included. Random‐effects models were applied to estimate pooled prevalence and odds ratios (ORs) for resistance. Subgroup analyses were performed by ethnicity: East Asians versus non‐East Asians to compare the differences in prevalence of gene variants.
Results
Ten studies comprising 1,614 CML patients were included. The pooled prevalence of BIM deletion was significantly higher in East Asians (12%, 95% CI: 10%–15%) compared to non‐East Asians (4%, 95% CI: 0%–11%, p = 0.025). Despite ethnic variability in frequency, BIM deletion was not significantly associated with imatinib resistance (OR 1.43, 95% CI 0.65–3.15, p = 0.37).
Conclusion
Although BIM deletion has a significantly higher prevalence in East Asian populations, pooled evidence does not support a statistically significant association with imatinib resistance. However, large, prospective, multi‐ethnic studies incorporating standardized response criteria and integrated molecular profiling will be essential to clarify whether BIM genotyping holds additive value in the risk stratification for TKI resistance.
Trial Registration
The authors have confirmed clinical trial registration is not applicable for this submission.