Association of genotypes and haplotypes of multi-drug transporter genes ABCB1 and ABCG2 with clinical response to imatinib mesylate in chronic myeloid leukemia patients

Au, Anthony; Baba, Abdul Aziz; Goh, Ai Sim; Fadilah, S A W; A, Teh; Hassan, Rosline; Ankathil, Ravindran

doi:10.1016/j.biopha.2014.01.009

Cited by 58 publications

(67 citation statements)

References 26 publications

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“…Our findings are in agreement with the study conducted by Au et al [45]. They suggested that ABCB1 3435C allele and ABCG2 421C allele are associated with poor response to imatinib therapy [45]. Similar to ABCB1 polymorphisms, there is a contradiction toward the impact of XRCC1 polymorphisms, especially Arg194Trp, on the occurrence of leukemia.…”

Section: Discussionsupporting

confidence: 92%

“…Furthermore, it has been shown that for evaluating of drug response, assessment of relation between the genotype and cytogenetic response has greater significance than relation between genotypes and hematological response [44]. Our findings are in agreement with the study conducted by Au et al [45]. They suggested that ABCB1 3435C allele and ABCG2 421C allele are associated with poor response to imatinib therapy [45].…”

Section: Discussionsupporting

confidence: 92%

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Concurrent effects of ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp genetic polymorphisms with risk of cancer, clinical output, and response to treatment with imatinib mesylate in patients with chronic myeloid leukemia

et al. 2015

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There are a paucity and contradicted data about the impact of concurrent heredity of polymorphic genes and risk of chronic myeloid leukemia (CML). In the present study, the concurrent effects of three polymorphisms affecting the integrity of DNA consist of ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp on development of chronic myeloid leukemia were studied. Furthermore, the role of these polymorphisms in clinical and laboratory outcomes of patients was evaluated. In this case-control study, 70 CML patients and 140 healthy individuals were enrolled in the study. The clinical features of patients such as phase of disease and response to treatment and laboratory data before and after treatment with imatinib mesylate were collected. ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp single nucleotide polymorphisms were evaluated by restriction fragment length polymorphism-polymerase chain reaction. The T allele of ABCB1 C3435T, T allele of XRCC1 Arg194Trp, and C allele of ABCG2 C421A polymorphisms were significantly higher in patients than controls. TT genotype of ABCB1 and TT genotype of XRCC1 were associated with higher risk of chronic myeloid leukemia development. CC421 ABCG2/TT3435 ABCB1 and CC421 ABCG2/TT27157 XRCC1 were also correlated with a higher risk of CML. Patients with C allele of ABCB1 had poor cytogenetic response, and correlation of CC421 ABCG2/TT3435 ABCB1 diplotype with accelerated phase of CML was significant. Patients with CC421 ABCG2/TT3435 ABCB1 and CC421 ABCG2/TT27157 XRCC1 diplotypes might be at higher risk to rapid and severe development of CML and have weaker response to treatments with imatinib.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Concurrent effects of ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp genetic polymorphisms with risk of cancer, clinical output, and response to treatment with imatinib mesylate in patients with chronic myeloid leukemia

et al. 2015

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“…This result is believed to be associated with the intracellular concentration of imatinib and is in agreement with the findings reported by Kim et al 42) In addition, several studies have reported that the ABCG2 421 A allele is associated with a significantly higher rate of MMR. [42][43][44] The involvement of multiple human transporters in imatinib pharmacokinetics makes the investigation of imatinib transport mechanisms difficult. However, among the various drug-transporters, BCRP appears to impart the strongest influence on imatinib exposure and clinical response.…”

Section: Imatinib Tdmmentioning

confidence: 99%

Therapeutic Drug Monitoring of Imatinib, Nilotinib, and Dasatinib for Patients with Chronic Myeloid Leukemia

Miura

2015

Biological & Pharmaceutical Bulletin

131

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Imatinib, nilotinib, and dasatinib are tyrosine kinase inhibitors (TKIs) that have become first-line treatments for Philadelphia chromosome-positive chronic myeloid leukemia (CML). According to European LeukemiaNet recommendations, the clinical response of CML patients receiving TKI therapy should be evaluated after 3, 6, and 12 months. For patients not achieving a satisfactory response within 3 months, the mean plasma concentration for the three months of TKI administration must be considered. In TKI therapy for CML patients, therapeutic drug monitoring is a new strategy for dosage optimization to obtain a faster and more effective clinical response. The imatinib plasma trough concentration (C 0 ) should be set above 1000 ng/mL to obtain a response and below 3000 ng/mL to avoid serious adverse events such as neutropenia. For patients with a UGT1A1*6/*6, *6/*28, or *28/*28 genotype initially administered 300-400 mg/d, a target nilotinib C 0 of 500 ng/mL is recommended to prevent elevation of bilirubin levels, whereas for patients with the UGT1A1*1 allele initially administered 600 mg/d, a target nilotinib C 0 of 800 ng/mL is recommended. For dasatinib, it is recommended that a higher C max or C 2 (above 50 ng/mL) to obtain a clinical response and a lower C 0 (less than 2.5 ng/mL) to avoid pleural effusion be maintained by once daily administration of dasatinib. Although at present clinicians consider the next pharmacotherapy from clinical responses (efficacy/ toxicity) obtained by a fixed dosage of TKI, the TKI dosage should be adjusted based on target plasma concentrations to maximize the efficacy and to minimize the incidence of adverse events.

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“…A further screening process excluded studies that were not casecontrol (N = 30), studies not relevant to IM (N = 48), studies unrelated to ABCB1 or MDR1 (N = 41), weakly correlated data in studies (N = 14), insufficient information in studies (N = 16). At the end of the selection process, a total of 10 articles, published between 2008 and 2014, and including 987 patients with CML, were finally selected for meta-analysis (Dulucq et al, 2008;Deenik et al, 2010;Kim et al, 2010;Marin et al, 2010;Takahashi et al, 2010;Ni et al, 2011;Elghannam et al, 2013;Seong et al, 2013;Au et al, 2014;Vivona et al, 2014). Of the 10 studies, 1 was performed in Africans, 4 were performed in Asians, and 5 in Caucasians.…”

Section: Literature Search Results and Baseline Characteristics Of Thmentioning

confidence: 99%

“…Although specific genotypes of genes involved in IM bioavailability seem to affect the function of the relative protein, there is still controversy regarding the role of MDR1 genetic variations in the response to IM therapy in patients with CML (Maffioli et al, 2011). While some studies have suggested that MDR1 genetic variations influence response to IM therapy in CML patients (Deenik et al, 2010;Seong et al, 2013;Vivona et al, 2012Vivona et al, , 2014, another study failed to find this correlation (Au et al, 2014). Moreover, few studies have focused on MDR1 and its relation with the clinical features or treatment responses in CML (Vasconcelos et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Multidrug resistance gene (MDR1) polymorphisms may not be directly associated with response to imatinib in chronic myeloid leukemia

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Our study aimed to investigate the association between multidrug resistance (MDR1) gene polymorphisms and the response to imatinib (IM) in chronic myeloid leukemia (CML). An electronic databases in PubMed, Cochrane Library, Wanfang, China National Knowledge Infrastructure, and VIP were searched using combinations of keywords relating to MDR1 polymorphisms and the response to IM in CML. Studies retrieved from database searches were screened using stringent inclusion and exclusion criteria. The Comprehensive Meta-analysis 2.0 software was utilized for all statistical analyses. In total, 186 studies were initially retrieved, and 10 studies, involving 987 CML patients, were eventually included in this meta-analysis. Results of our study revealed no significant associations between MDR1 rs1045642, rs1128503, and rs2032582 polymorphisms and major molecular response and complete molecular 14967-14978 (2015) response in CML patients. Significant differences were observed in the genotype frequencies of MDR1 rs1128503 under homozygous, heterozygous, and recessive models, between CML patients sensitive and resistant to IM. A significant difference in genotype frequencies of MDR1 rs2032582 was also observed under allele, homozygous, heterozygous, and recessive models between CML patients sensitive and resistant to IM. In conclusion, based on our meta-analysis, the MDR1 polymorphisms, rs1045642, rs1128503, and rs2032582, are not directly correlated with the curative effect of IM treatment of CML patients.

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Association of genotypes and haplotypes of multi-drug transporter genes ABCB1 and ABCG2 with clinical response to imatinib mesylate in chronic myeloid leukemia patients

Cited by 58 publications

References 26 publications

Concurrent effects of ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp genetic polymorphisms with risk of cancer, clinical output, and response to treatment with imatinib mesylate in patients with chronic myeloid leukemia

Concurrent effects of ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp genetic polymorphisms with risk of cancer, clinical output, and response to treatment with imatinib mesylate in patients with chronic myeloid leukemia

Therapeutic Drug Monitoring of Imatinib, Nilotinib, and Dasatinib for Patients with Chronic Myeloid Leukemia

Multidrug resistance gene (MDR1) polymorphisms may not be directly associated with response to imatinib in chronic myeloid leukemia

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