<i>MDR1</i> gene polymorphisms and imatinib response in chronic myeloid leukemia: A meta-analysis

Louati, Nour; Turki, F.; Mnif, Héla; Frikha, Rim

doi:10.1177/1078155220981150

Cited by 6 publications

(5 citation statements)

References 39 publications

(54 reference statements)

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“…TKI efficacy is highly dependent on cellular drug concentration to effectively block BCR-ABL activity, and low TKI concentrations have already been associated, at least in part, with reduced expression or activity of SLC transporters and/or increased expression or activity of ABC transporters [ 40 , 41 ]. The SNVs studied here, which are associated with altered expression and activity, have a potential role in response to therapy [ 42 , 43 ]. Recently Rajamani et al showed the influences of ABCB1 polymorphisms and plasma imatinib levels on early molecular response and failure-free survival [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Variants of ABC and SLC Transporter Genes and Chronic Myeloid Leukaemia: Impact on Susceptibility and Prognosis

Alves

Gonçalves

Jorge

et al. 2022

IJMS

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Solute carrier (SLC) and ATP-binding cassette (ABC) transporters comprise a variety of proteins expressed on cell membranes responsible for intrusion or extrusion of substrates, respectively, including nutrients, xenobiotics, and chemotherapeutic agents. These transporters mediate the cellular disposition of tyrosine kinase inhibitors (TKIs), and their genetic variants could affect its function, potentially predisposing patients to chronic myeloid leukaemia (CML) and modulating treatment response. We explored the impact of genetic variability (single nucleotide variants—SNVs) of drug transporter genes (ABCB1, ABCG2, SLC22A1, and SLC22A5) on CML susceptibility, drug response, and BCR-ABL1 mutation status. We genotyped 10 SNVs by tetra-primers-AMRS-PCR in 198 CML patients and 404 controls, and assessed their role in CML susceptibility and prognosis. We identified five SNVs associated with CML predisposition, with some variants increasing disease risk, including TT genotype ABCB1 (rs1045642), and others showing a protective effect (GG genotype SLC22A5 rs274558). We also observed different haplotypes and genotypic profiles associated with CML predisposition. Relating to drug response impact, we found that CML patients with the CC genotype (rs2231142 ABCG2) had an increased risk of TKI resistance (six-fold). Additionally, CML patients carrying the CG genotype (rs683369 SLC22A1) presented a 4.54-fold higher risk of BCR-ABL1 mutations. Our results suggest that drug transporters’ SNVs might be involved in CML susceptibility and TKI response, and predict the risk of BCR-ABL1 mutations, highlighting the impact that SNVs could have in therapeutic selection.

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Section: Discussionmentioning

confidence: 99%

Genetic Variants of ABC and SLC Transporter Genes and Chronic Myeloid Leukaemia: Impact on Susceptibility and Prognosis

Alves

Gonçalves

Jorge

et al. 2022

IJMS

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“…The association between of the MDR1 gene (C1236T, G2677T/A, and C3435T SNPs) and IM resistance acquisition in CML patients was extensively studied and meta-analyzed [14] [25] [26]. A recent meta-analysis (2021) concluded that MDR1 SNPs genotypes are not significantly related to the IM response in patients with CML [26], which is contrary to some previous studies that showed genetic variations were associated with the increasing risk of resistance to IM in CML patients [17] [24]. These heterogeneous results illustrate a potential role of ethnicity in the genetic context [32].…”

Section: Discussionmentioning

confidence: 99%

“…MDR1 is a highly polymorphic gene with at least 50 SNPs. Some of these SNPs have been extensively studied in CML disease: two silent SNPs C1236T (rs1128503), and C3435T (rs1045642) in the exon 12 and 26, respectively; and one missense SNP G2677T/A (rs2032582) located in exon 21 [14] [16]- [26]. However, although various attempts to explain the impact of the MDR1 variants on IM efficacy in patients with CML, the outcomes remain contradictor rather than conclusive.…”

Section: Introductionmentioning

confidence: 99%

MDR1 Haplotypes and G2677T/A Polymorphism Predict Imatinib Response in Tunisian Patients with Chronic Myeloid Leukemia

Ammar¹,

Ktari²,

Medhaffar³

et al. 2022

JBM

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Background: The role of human multidrug resistance gene (MDR1) SNPs in the interindividual variability of imatinib mesylate (IM) response has received considerable attention. We aimed to study the association between SNPs of the MDR1 gene (C1236T, G2677T/A, C3435T) and IM response in chronic myeloid leukemia (CML) patients. Method: A retrospective case-control study was conducted on 48 patients with CML undergoing IM therapy. All patients were genotyped using PCR-RFLP method. Results: The genotype and allele frequencies of C1236T and C3435T were not significantly different between CML patients responders and non-responders to IM (p > 0.05). The frequencies of 2677T allele and 2677TT genotype were significantly increased in CML patients IM responders which as compared with IM non-responders (50% vs 26.9%, p = 0.013 and 27.3% vs 3.8%, p = 0.029 respectively). Whereas the 2677AA genotype and CAC haplotype were found only in CML patients IM non-responders (15.4%). Conclusion: Pretreatment genotyping of G2677A/T appears to be useful for predicting IM resistance, which may allow the best choice of drug treatment for CML patients.

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“…Chronic myeloid leukemia (CML) is a multifactorial clonal myeloid neoplasm originating from malignant hematopoietic stem cells [1][2][3] with an approximate incidence of one to two per 100,000 adults worldwide [4]. The reciprocal translocation (t (9; 22) (q34; q11)) resulting in the Philadelphia (Ph) chromosome formation is pivotal to the pathogenesis of CML [8].…”

Section: Introductionmentioning

confidence: 99%

Effects of ABCG2 C421A and ABCG2 G34A genetic polymorphisms on clinical outcome and response to imatinib mesylate, in Iranian chronic myeloid leukemia patients

Nouri

Mehrzad

Khalaj

et al. 2023

Egypt J Med Hum Genet

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Background Chronic myeloid leukemia (CML) is a multifactorial clonal myeloid neoplasm that mainly arises from the Philadelphia chromosome. Even though imatinib mesylate (IM) is considered the gold standard for first-line treatment, a number of CML patients have shown IM resistance that can be influenced by many factors, including pharmacogenetic variability. The present study examined whether two common single nucleotide polymorphisms (SNPs) of ABCG2 (G34A and C421A) contribute to IM resistance and/or good responses. Material and methods A total of 72 CML patients were genotyped with high-resolution melting (HRM) and restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). We also determined the cytogenetic and hematological response, as evaluable factors for measuring response to imatinib. Results In the current study, we explored the relationship between the different variants of ABCG2 G34A and C421A and clinical response to imatinib among CML patients. There were no statistically significant differences between genotypes of C421A and G34A and allele frequencies among the resistant and responder groups, with response to IM (P > 0.05). Also, we found no statistically significant association between genotypes and cytogenetic and hematological responses. Conclusion This is the first study to investigate the association between genotypes of the G34A and C421A SNPs and the outcome of IM treatment in Iranian population. As a whole, genotyping of these SNPs is unhelpful in predicting IM response in CML patients.

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MDR1 gene polymorphisms and imatinib response in chronic myeloid leukemia: A meta-analysis

Cited by 6 publications

References 39 publications

Genetic Variants of ABC and SLC Transporter Genes and Chronic Myeloid Leukaemia: Impact on Susceptibility and Prognosis

Genetic Variants of ABC and SLC Transporter Genes and Chronic Myeloid Leukaemia: Impact on Susceptibility and Prognosis

MDR1 Haplotypes and G2677T/A Polymorphism Predict Imatinib Response in Tunisian Patients with Chronic Myeloid Leukemia

Effects of ABCG2 C421A and ABCG2 G34A genetic polymorphisms on clinical outcome and response to imatinib mesylate, in Iranian chronic myeloid leukemia patients

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