21 results on '"Zhao, Xie-Lan"'
Search Results
2. A validated UPLC–MS/MS method for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma
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Zeng, Jing, Cai, Hua lin, Jiang, Zhi ping, Wang, Qing, Zhu, Yan, Xu, Ping, and Zhao, Xie lan
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- 2017
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3. Roles of hsa-miR-12462 and SLC9A1 in acute myeloid leukemia
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Jia, Yan, Liu, Wei, Zhan, Hui-En, Yi, Xiao-Ping, Liang, Hui, Zheng, Qi-Li, Jiang, Xin-Ya, Zhou, Hai-Yan, Zhao, Liang, Zhao, Xie-Lan, and Zeng, Hui
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- 2020
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4. Role of HMGB1 in regulation of STAT3 expression in CD4+ T cells from patients with aGVHD after allogeneic hematopoietic stem cell transplantation
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Xu, Ya-jing, Li, Lin, Chen, Yan, Fu, Bin, Wu, Deng-shu, Li, Xiao-lin, Zhao, Xie-lan, and Chen, Fang-ping
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- 2015
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5. Influence of DNMT3A R882 mutations on AML prognosis determined by the allele ratio in Chinese patients
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Yuan, Xiao-Qing, Chen, Peng, Du, Yin-Xiao, Zhu, Ke-Wei, Zhang, Dao-Yu, Yan, Han, Liu, Han, Liu, Yan-Ling, Cao, Shan, Zhou, Gan, Zeng, Hui, Chen, Shu-Ping, Zhao, Xie-Lan, Yang, Jing, Zeng, Wen-Jing, and Chen, Xiao-Ping
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- 2019
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6. Influence of UGT1A1 polymorphisms on the outcome of acute myeloid leukemia patients treated with cytarabine-base regimens
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Chen, Peng, Zhu, Ke-Wei, Zhang, Dao-Yu, Yan, Han, Liu, Han, Liu, Yan-Ling, Cao, Shan, Zhou, Gan, Zeng, Hui, Chen, Shu-Ping, Zhao, Xie-Lan, Yang, Jing, and Chen, Xiao-Ping
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- 2018
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7. Association of genetic polymorphisms in genes involved in Ara-C and dNTP metabolism pathway with chemosensitivity and prognosis of adult acute myeloid leukemia (AML)
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Zhu, Ke-Wei, Chen, Peng, Zhang, Dao-Yu, Yan, Han, Liu, Han, Cen, Li-Na, Liu, Yan-Ling, Cao, Shan, Zhou, Gan, Zeng, Hui, Chen, Shu-Ping, Zhao, Xie-Lan, and Chen, Xiao-Ping
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- 2018
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8. Inactivation of PTEN increases ABCG2 expression and the side population through the PI3K/Akt pathway in adult acute leukemia
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Huang, Fang-Fang, Wu, Deng-Shu, Zhang, Li, Yu, Yan-Hui, Yuan, Xiao-Yu, Li, Wen-Jin, Chen, Xiao-Ping, Zhao, Xie-Lan, Chen, Fang-Ping, and Zeng, Hui
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- 2013
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9. Changing Treatment May Affect the Predictive Ability of European Treatment Outcome Study Scoring for the Prognosis of Patients with Chronic Myeloid Leukemia
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Chen Fang-ping, He Qun, Jing Huang, Lu Chen, Zhao Xie-lan, Leyan Wang, and Xu Yajing
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0301 basic medicine ,Oncology ,Adult ,Male ,medicine.medical_specialty ,lcsh:Internal medicine ,Treatment outcome ,Antineoplastic Agents ,Kaplan-Meier Estimate ,Affect (psychology) ,Disease-Free Survival ,Drug Administration Schedule ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Statistical significance ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,medicine ,Hasford score ,Humans ,Hydroxyurea ,lcsh:RC31-1245 ,Retrospective Studies ,business.industry ,lcsh:RC633-647.5 ,Myeloid leukemia ,Retrospective cohort study ,Imatinib ,Hematology ,lcsh:Diseases of the blood and blood-forming organs ,Middle Aged ,medicine.disease ,Prognosis ,Europe ,Leukemia ,030104 developmental biology ,Imatinib mesylate ,Treatment Outcome ,030220 oncology & carcinogenesis ,European Treatment Outcome Study Score ,Imatinib Mesylate ,Female ,business ,Sokal score ,medicine.drug ,Research Article - Abstract
Previous studies compared the predictive ability of the European Treatment Outcome Study (EUTOS), Sokal, and Hasford scoring systems and demonstrated inconsistent findings with unknown reasons. This study was conducted to determine a useful scoring system to predict the prognosis of patients with chronic myeloid leukemia (CML) and identify the probable factors that affect the scoring.This is a retrospective cohort study. The predictive ability of EUTOS and the factors that affect scoring were analyzed in 234 Chinese chronic-phase CML patients treated with frontline imatinib, including a few patients temporarily administered hydroxyurea for cytoreduction before imatinib. Patients were stratified into different risk groups according to each scoring system to assess the treatment outcomes and the predictive ability of EUTOS scores between patients who received imatinib during the entire follow-up period and patients who received altered treatment because of intolerance, progression, and treatment failure.Sixty-one (26.0%) patients received altered treatments during the follow-up. In the EUTOS low- and high-risk groups, the 5-year overall survival was 94.6% and 84.7% (p=0.011), 5-year event-free survival was 92.6% and 77.6% (p=0.001), and 5-year progression-free survival (PFS) was 95.3% and 82.4% (p=0.001), respectively. The predictive ability of EUTOS was better than that of the Sokal and Hasford scores (p=0.256, p=0.062, p=0.073) without statistical significance. All three scoring systems were valid in predicting early optimal response. Kaplan-Meier analysis showed a high association between overall PFS and the EUTOS scores in the standard-dose imatinib group (p0.001).This study suggests that the EUTOS scoring system could predict the outcome of chronic-phase CML patients treated with standard-dose imatinib. Altered treatment is a crucial factor that affects the prognostic impact of EUTOS scoring. Achieving complete cytogenetic response at 18 months is an essential factor in predicting the prognosis of patients with CML.Amaç: Avrupa Tedavi İzlem Çalışması (EUTOS), Sokal ve Hasford skorlamalarının öngörüsel tahmin başarılarının karşılaştırıldığı çalışmalarda bilinmeyen nedenlerle tutarsız bulgular görülmektedir. Bu çalışma, kronik miyeloid lösemi (KML) hastalarının prognozunu tahmin edecek yararlı bir skorlama sistemi bulma ve skorlamayı etkileyen muhtemel faktörleri ortaya çıkartmak amacıyla yapılmıştır. Gereç ve Yöntemler: Bu çalışma geriye dönük hasta grubunda yapılmıştır. İmatinib tedavisi gören 234 Çinli kronik faz KML hastasında (birkaç hasta imatinib tedavisi öncesi kısa süreli hidroksiüre tedavisi almıştır) EUTOS tahmin skorları ve bu skorlamayı etkileyen faktörler incelenmiştir. Tedavi çıktılarını ve EUTOS skorlarının tahmin başarısını belirlemek amacıyla tüm izlem boyunca imatinib alan ve intolerans, ilerleme ya da tedavi başarısızlığı gibi nedenlerle farklı tedaviler alan hastalar, her skorlama sistemine göre değişik risk gruplarında sınıflandırılmıştır. Bulgular: Takip sürecinde hastaların 61 tanesinde (%26) tedavi değişikliği olmuştur. EUTOS düşük ve yüksek risk gruplarında 5 yıllık genel sağkalım sırasıyla %94,6 ve %84,7 (p=0,011), hastalıksız sağkalım %95,3 ve %82,4 (p=0,001) ve progresyonsuz sağkalım %95,3 ve %77,6 (p=0,001) olarak bulunmuştur. EUTOS tahminleri, istatistiksel olarak anlamlı olmamakla beraber, Sokal ve Hasford skorlarından daha iyi görülmektedir (p=0,256, p=0,062, p=0,073). Her üç skorlama da erken optimal yanıtın değerlendirmesinde geçerli görülmektedir. Kaplan-Meier analizleri, standart doz imatinib kullanılan gruplarda, genel progresyonsuz sağkalım ve EUTOS skorları arasında yüksek anlamlılıkta bir ilişki göstermektedir (p0,001). Sonuç: Bu çalışma EUTOS skorlama tahmin sisteminin, standart-doz imatinib ile tedavi edilen kronik faz KML hastalarının yanıtlarının değerlendirmesinde uygun olduğunu göstermektedir. Tedavi değişikliği, EUTOS skorlamasının prognostik değerlendirme sonucunu etkileyen önemli bir faktördür. KML hastalarının prognoz tahminleri etkileyen bir diğer önemli faktör de 18. ayda tam sitogenetik yanıta ulaşılmasıdır.
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- 2017
10. Meta-Analysis of the Effect of MDR1 C3435T Polymorphism on Cyclosporine Pharmacokinetics
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Jiang, Zhi-Ping, Wang, Yi-Ren, Xu, Ping, Liu, Rong-Rong, Zhao, Xie-Lan, and Chen, Fang-Ping
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- 2008
11. CDK6 Is a Potential Prognostic Biomarker in Acute Myeloid Leukemia.
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Liu, Wei, Yi, Jin-Mou, Liu, Yi, Chen, Cong, Zhang, Kai-Xuan, Zhou, Cheng, Zhan, Hui-En, Zhao, Liang, Morales, Stephanie, Zhao, Xie-Lan, and Zeng, Hui
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ACUTE myeloid leukemia ,MESSENGER RNA ,BIOMARKERS ,DIAGNOSIS ,GENES - Abstract
Acute myeloid leukemia (AML) is a threatening hematological malignant disease in which new successful approaches in therapy are needed. Cyclin-dependent kinase 6 (CDK6), a regulatory enzyme of the cell cycle that plays an important role in leukemogenesis and the maintenance of leukemia stem cells (LSC), has the potential to predict the prognosis of AML. By analyzing public databases, we observed that the messenger RNA (mRNA) levels of CDK6 were significantly overexpressed in AML cell lines and non-acute promyelocytic leukemia (non-APL) AML patients when compared to healthy donors. Furthermore, CDK6 expression was significantly reduced in AML patients who achieved complete remission (CR) compared to that at the time of diagnosis in our validated cohort. The expression of CDK6 was tightly correlated with peripheral blood blasts, French–American–British (FAB) subtypes, CCAAT-enhancer-binding protein α (CEBPA) mutation, and chromosomal abnormalities of t(8;21). However, the clinical significance and effects of CDK6 expression on the prognosis of non-APL AML patients remain uncertain. We found that CDK6 expression was inversely correlated with overall survival (OS) among non-APL AML patients using the Kaplan–Meier analysis. CDK6 was also found to be positively associated with genes identified to contribute to the development of leukemia, including CCND2 , DNMT3B , SOX4 , and IKZF2 , as well as being negatively associated with anticancer microRNAs, including miR-187, miR-9, miR-582, miR708, and miR-362. In summary, our study revealed that CDK6 might be a potential diagnostic and prognostic biomarker in non-APL AML patients. [ABSTRACT FROM AUTHOR]
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- 2021
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12. Chidamide acts on the histone deacetylase‐mediated miR‐34a/Bcl‐2 axis to regulate NB4 cell line proliferation and apoptosis.
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Peng, Jie, Li, Shu‐Jun, Fu, Xiao, Liu, Yi, and Zhao, Xie‐Lan
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APOPTOSIS ,ACUTE promyelocytic leukemia ,RETINOIC acid receptors ,ACUTE myeloid leukemia ,CELL proliferation ,INTERLEUKIN-21 ,ARSENIC trioxide - Abstract
Acute promyelocytic leukemia (APL), a biologically and clinically distinct variant of acute myelogenous leukemia, is characterized by the fusion of the N‐terminus of promyelocytic leukemia protein to the C terminus of retinoic acid receptor alpha, mostly due to chromosomal translocation t(15;17). Chidamide, a synthetic analogue of MS‐275 identified from a group of benzamide‐type compounds, has been found to have efficient anticancer activity in basic and clinical research studies. However, the concrete role and underlying mechanism of Chidamide in the treatment of APL has not been well characterized. Our data demonstrate that Chidamide inhibited the expression of histone deacetylase (HDAC) to induce apoptosis and suppress proliferation in NB4 cells. Mechanistically, Chidamide increases the expression of miR‐34a by suppressing HDAC. Furthermore, B‐cell lymphoma‐2 (Bcl‐2) is a direct target of miR‐34a, the expression of which is regulated by miR‐34a. Functionally, Chidamide inhibits cell proliferation and promotes apoptosis through miR‐34a/Bcl‐2. Chidamide exerts its anticancer effect via the HDAC‐mediated miR‐34a/Bcl‐2 axis, providing potential targets for APL therapy. [ABSTRACT FROM AUTHOR]
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- 2020
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13. High Expression of AHSP, EPB42, GYPC and HEMGN Predicts Favorable Prognosis in FLT3-ITD-Negative Acute Myeloid Leukemia.
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Zhu, Gang-Zhi, Yang, Yong-Long, Zhang, Yan-Jiao, Liu, Wei, Li, Mu-Peng, Zeng, Wen-Jing, Zhao, Xie-Lan, and Chen, Xiao-Ping
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ACUTE myeloid leukemia ,PROTEIN-tyrosine kinases ,GENE expression ,BIOMARKERS ,PROTEIN microarrays - Abstract
Background/Aims: Acute myeloid leukemia (AML) is a heterogeneous clonal disease and patients with AML who harbor an FMS-like tyrosine kinase 3 (FLT3) mutation present several dilemmas for the clinician. This study aims to identify novel targets for explaining the dilemmas. Methods: We analyzed four microarray gene expression profiles to investigate changes in whole genome expression associated with FLT3-ITD mutation. Results: We identified 22 differentially expressed genes which are commonly expressed among all four profiles. Kaplan-Meier analysis of the dataset GSE12417 revealed that low expression of AHSP, EPB42, GYPC and HEMGN predicted poor prognosis (AHSP: P=0.0317, HR=1.894; EPB42: P=0.0382, HR=1.859; GYPC: P=0.0015, HR=2.051; HEMGN: P=0.0418, HR=1.838 in GSE12417 test cohort; AHSP: P=0.0279, HR=1.548; EPB42: P=0.0398, HR=1.505; GYPC: P=0.0408, HR=1.501; HEMGN: P=0.0143, HR=1.630 in GSE12417 validation cohort). When patients were FLT3-ITD positive, the expression of FLT3 was significantly increased (all P<0.05 in four profiles), and correleation analysis of four profiles revealed that the expression of the four candidate genes negatively correlated with FLT3 expression. Conclusions: Our findings suggest that AHSP, EPB42, GYPC and HEMGN may be suitable biomarkers for diagnostic or therapeutic strategies for FLT3-ITD-positive AML patients. [ABSTRACT FROM AUTHOR]
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- 2017
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14. PTEN Regulates BCRP/ABCG2 and the Side Population through the PI3K/Akt Pathway in Chronic Myeloid Leukemia.
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Huang, Fang-Fang, Zhang, Li, Wu, Deng-Shu, Yuan, Xiao-Yu, Chen, Fang-Ping, Zeng, Hui, Yu, Yan-Hui, and Zhao, Xie-Lan
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PHOSPHATIDYLINOSITOL 3-kinases ,PROTEIN kinase B ,CHRONIC myeloid leukemia ,POPULATION biology ,CANCER stem cells ,PHOSPHATASES - Abstract
A small population of cancer stem cells named the “side population” (SP) has been demonstrated to be responsible for the persistence of many solid tumors. However, the role of the SP in leukemic pathogenesis remains controversial. The resistance of leukemic stem cells to targeted therapies, such as tyrosine kinase inhibitors (TKIs), results in therapeutic failure or refractory/relapsed disease in chronic myeloid leukemia (CML). The drug pump, ATP-binding cassette sub-family G member 2 (ABCG2), is well known as a specific marker of the SP and could be controlled by several pathways, including the PI3K/Akt pathway. Our data demonstrated that compared with wild-type K562 cells, the higher percentage of ABCG2+ cells corresponded to the higher SP fraction in K562/ABCG2 (ABCG2 overexpressing) and K562/IMR (resistance to imatinib) cells, which exhibited enhanced drug resistance along with downregulated phosphatase and tensin homologue deleted on chromosome -10 (PTEN) and activated phosphorylated-Akt (p-Akt). PTEN and p-Akt downregulation could be abrogated by both the PI3K inhibitor LY294002 and the mTOR inhibitor rapamycin. Moreover, in CML patients in the accelerated phase/blastic phase (AP/BP), increased SP phenotype rather than ABCG2 expression was accompanied by the loss of PTEN protein and the up-regulation of p-Akt expression. These results suggested that the expression of ABCG2 and the SP may be regulated by PTEN through the PI3K/Akt pathway, which would be a potentially effective strategy for targeting CML stem cells. [ABSTRACT FROM AUTHOR]
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- 2014
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15. Hypothesizing that histone deacetylase inhibitors can be used to reverse multiple drug resistance.
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Jiang, Zhi-Ping, Xu, Ping, Wang, Guan-Ping, Zhao, Xie-Lan, and Chen, Fang-Ping
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HISTONE deacetylase ,ENZYME inhibitors ,MULTIDRUG resistance ,CANCER treatment ,P-glycoprotein ,HYPOTHESIS ,GENE expression - Abstract
Summary: It is well known that the mechanism of action of chemotherapeutic drugs and their ability to induce multidrug resistance (MDR) are of relevance to cancer treatment. Although MDR is a multifactorial process, the main obstacle is the expression of multidrug-efflux pumps that lowers the intracellular drug levels. P-glycoprotein (P-gp) is the longest identified efflux pump. Thus, P-gp has been looked as a well established mediator of MDR and it became a therapeutic target for circumventing multidrug resistance. However, the mechanism of adjusting the expression of P-gp is not clear yet. The results of the effect of genetic polymorphism on P-gp expression and function remain conflicting. More recently, studies on the regulation of MDR1 has widened to examine the role of epigenetics and some new results were found to support the effect of epigenetic variance in vitro. It is hence hypothesized that epigenetic variants play more important roles than genetic polymorphism, thus adjusting the epigenetic factors could alter the expression of MDR, leading to the reverse of MDR. And it is further hypothesized that histone deacetylase inhibitors could be another strategy to overcome MDR. The mechanism may include a bidirectional modulation of P-gp by histone deacetylase inhibitors. [Copyright &y& Elsevier]
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- 2010
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16. TBC1D16 predicts chemosensitivity and prognosis in adult acute myeloid leukemia (AML) patients.
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Liu, Han, Chen, Peng, Yang, Yong-Long, Zhu, Ke-Wei, Wang, Tao, Tang, Ling, Liu, Yan-Ling, Cao, Shan, Zhou, Gan, Zeng, Hui, Zhao, Xie-Lan, Zhang, Wei, and Chen, Xiao-Ping
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ACUTE myeloid leukemia , *PROGNOSIS , *DNA methylation , *GENES , *NUCLEOTIDE sequencing , *BREAST cancer prognosis - Abstract
Acute myeloid leukemia (AML) is a hematopoietic disease with poor survival. Chemotherapy resistance is one of the determinant factors influencing AML prognosis. To identify genes possibly affecting the drug responses in AML, the Illumina Infinium MethylationEPIC (850K) was used to screen for differential DNA methylation loci between patients achieved complete remission (CR) or not (non-CR) after induction therapy in 37 AML patients. Then, 32 differentially methylated sites (DMS) were selected for replication in another 86 AML patients by next-generation sequencing. Nine sites including cg03988660, cg16804603, cg18166936, cg11308319, cg09095403, cg18493214, cg01443536, cg16030878 and cg10143426 were replicated. Analysis of the Gene Expression Omnibus (GEO) database showed that mRNA expression of TBC1D16 and HDAC4 was associated with AML prognosis. Methylation level of the cg16030878 in TBC1D16 3′-UTR correlated positively with TBC1D1 6 mRNA expression in samples both in the TCGA database and clinically collected in the study. Both higher cg16030878 methylation and higher TBC1D1 6 mRNA expression were associated with increased risk of non-CR and worse overall survival (OS) in AML patients. In AML cells, knockdown of TBC1D16 decreased cell proliferation and ERK phosphorylation levels, as well as increased sensitivity to mitoxantrone and decitabine indicated by IC 50. In patients with combined use of decitabine, those patients with CR showed significantly lower TBC1D1 6 mRNA expression. On the contrary, knockdown of TBC1D16 resulted in decreased sensitivity to cytarabine in U937 cells. Our findings implicated that TBC1D16 is a potential predictor for chemosensitivity and prognosis in adult AML patients. [ABSTRACT FROM AUTHOR]
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- 2021
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17. Down-regulating NQO1 promotes cellular proliferation in K562 cells via elevating DNA synthesis.
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Xiao, Fei-Yan, Jiang, Zhi-Ping, Yuan, Fang, Zhou, Fang-Jiao, Kuang, Wei, Zhou, Gan, Chen, Xiao-Ping, Liu, Rong, Zhou, Hong-Hao, Zhao, Xie-Lan, and Cao, Shan
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CELL proliferation , *CHRONIC myeloid leukemia , *CELL growth , *PROTEIN expression - Abstract
NQO1 protein acts as a cellular protective system, on account of its role as a quinone reductase and redox regulator. Nonetheless, new NQO1 roles are emerging—including its regulation of the cellular proliferation of many tumor cells—and this enzyme has been found to relate to the incidence of various diseases, including chronic myeloid leukemia. However, the mechanisms through which NQO1 influences leukemia progression remain unclear. The current study looks to name NQO1 as a novel molecular target that modulates DNA synthesis and chronic myeloid leukemia growth. Our results indicate that the frequency of the T allele of NQO1 polymorphism in chronic myeloid leukemia patients is higher than that among healthy East Asian individuals (0.492 vs. 0.419) and much higher than the average level of the general population (0.492 vs. 0.289) (1000 Genomes). Functionally, NQO1 knockdown increases the protein expression of the TOP2A and MCM complex, and consequently promotes DNA synthesis and K562 cell growth. NQO1 knockdown also promotes tumorigenesis in a xenograft model. NQO1 overexpression, on the other hand, was found to have the opposite effects. Our results show that NQO1 downregulation promotes K562 cellular proliferation via the elevation of DNA synthesis. [ABSTRACT FROM AUTHOR]
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- 2020
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18. Effects of Trough Concentration and Solute Carrier Polymorphisms on Imatinib Efficacy in Chinese Patients with Chronic Myeloid Leukemia.
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Wang Q, Jiang ZP, Zeng J, Zhu Y, Cai HL, Xiang DX, He Q, Shi XL, Zhong AN, Zhao XL, and Xu P
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- Adolescent, Adult, Aged, Aged, 80 and over, Asian People genetics, Female, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Treatment Outcome, Young Adult, Antineoplastic Agents blood, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents therapeutic use, Imatinib Mesylate blood, Imatinib Mesylate pharmacokinetics, Imatinib Mesylate therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism, Membrane Transport Proteins genetics, Neoplasm Proteins genetics, Protein Kinase Inhibitors blood, Protein Kinase Inhibitors pharmacokinetics, Protein Kinase Inhibitors therapeutic use
- Abstract
Purpose: We investigated the relationship between imatinib trough concentrations and genetic polymorphisms with efficacy of imatinib in Chinese patients with chronic myeloid leukemia (CML)., Methods: There were 171 eligible patients. Peripheral blood samples were collected from 171 eligible patients between 21 and 27 hours after the last imatinib administration. Complete cytogenetic response (CCyR), major molecular response (MMR) and complete molecular response (CMR) were used as metrics for efficacy. Nine single nucleotide polymorphisms in 5 genes, SLC22A4 (917 T>C, -248 C>G and -538 C>G), SLC22A5 (-945 T>G and -1889 T>C), SLCO1A2 (-361 G>A), SLCO1B3 (334 T>G and 699 G>A) and ABCG2 (421C>A) were selected for genotyping., Results: Patients with CCyR achieve higher trough concentrations than those without CCyR (1478.18±659.83 vs 984.89±454.06 ng mL-1, p<0.001). Patients with MMR and CMR achieve higher trough concentrations than those without MMR and CMR, respectively (1486.40±703.38 vs 1121.17±527.14 ng mL-1, p=0.007; 1528.00±709.98 vs 1112.67±518.35 ng mL-1, p=0.003, respectively). Carriers of A allele in SLCO1A2 -361G>A achieve higher CCyR and MMR rates (p=0.047, OR=4.320, 95% CI: 0.924-20.206; p=0.042, OR=2.825, 95% CI: 1.016-7.853, respectively). Both trough concentrations and SLCO1A2 -361G>A genotypes are independent factors affecting imatinib efficacy. The positive and negative predictive values for CCyR are 71.01% and 68.75%, respectively. The positive and negative predictive values for MMR are 62.86% and 69.70%, respectively., Conclusion: Imatinib trough concentrations and SLCO1A2 -361G>A genotypes are associated with imatinib efficacy in Chinese patients with CML.
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- 2020
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19. Population pharmacokinetic and pharmacogenetics of imatinib in Chinese patients with chronic myeloid leukemia.
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Wang Q, Jiang ZP, Yu EQ, Zeng J, Zhu Y, Cai HL, Yan M, Xiang DX, Zhao XL, Xu P, Jiao Z, and Banh HL
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- Adult, China epidemiology, Female, Humans, Imatinib Mesylate administration & dosage, Imatinib Mesylate pharmacokinetics, Kinetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Male, Middle Aged, Biological Variation, Population, Imatinib Mesylate blood, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Pharmacogenetics
- Abstract
Aim: This study aimed to establish a population pharmacokinetic (PPK) model in Chinese patients with chronic myeloid leukemia, and to quantify the effects of pharmacogenetics on pharmacokinetic parameters of imatinib., Methods: A total of 229 plasma concentrations from 170 patients were analyzed. Nonlinear mixed effect model was used to establish the PPK model., Results: A one-compartment model with first-order absorption and first-order elimination adequately describes imatinib pharmacokinetics. Actual bodyweight shows slight effect on the estimated apparent clearance (CL/F) of imatinib in this study population. The final PPK model is: K
a (1/h) = 0.329; CL/F (l/h) = 9.25 × (actual bodyweight/70)0.228 ; V/F(l) = 222., Conclusion: Actual bodyweight has a slight effect on CL/F. Demographics, physiopathology and pharmacogenetics covariates have no significant effects on imatinib pharmacokinetics.- Published
- 2019
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20. Trough concentration and ABCG2 polymorphism are better to predict imatinib response in chronic myeloid leukemia: a meta-analysis.
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Jiang ZP, Zhao XL, Takahashi N, Angelini S, Dubashi B, Sun L, and Xu P
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- Antineoplastic Agents blood, Antineoplastic Agents pharmacology, Asian People genetics, Humans, Imatinib Mesylate blood, Imatinib Mesylate pharmacology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood, Polymorphism, Single Nucleotide drug effects, Predictive Value of Tests, Treatment Outcome, ATP Binding Cassette Transporter, Subfamily G, Member 2 genetics, Antineoplastic Agents therapeutic use, Imatinib Mesylate therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Neoplasm Proteins genetics, Polymorphism, Single Nucleotide genetics
- Abstract
Aim: The present study aimed to conduct a series of meta-analyses to investigate the influence of imatinib trough concentration (C
0 ), as well as ABCB1 and ABCG2 polymorphisms, on the clinical response in patients with chronic myeloid leukemia (CML)., Methods: A literature search was conducted using the PubMed and Cochrane electronic databases to locate relevant papers from 2003 onward. Then, an initial meta-analysis of 14 studies involving 2184 patients was conducted to understand the effect of imatinib mesylate (IM) C0 on clinical outcome in CML patients. Subsequently, a series of meta-analyses were performed, including up to 23 studies with 2577 patients, on the effect of genetic polymorphisms of ABCB1 and ABCG2 on the clinical response to IM., Results: Meta-analysis revealed that patients who achieved a major molecular response (MMR) have a significantly higher IM C0 than those who failed to achieve an MMR. We also found that the patients who achieved a complete cytogenic response (CCyR) have a significantly higher IM C0 than those who did not achieve a CCyR. However, no significant difference in IM C0 was found between the complete molecular response and non-complete molecular response groups. Additional analysis showed that ABCG2 421 variant A allele was significantly associated with a higher rate of MMR and overall response, especially in Asian patients. Meta-analysis did not reveal a correlation between ABCB1 C3435T and C1236T polymorphisms with any clinical response to IM. However, the G2677T/A polymorphism could play a role in IM response in the recessive model., Conclusion: This meta-analysis demonstrates that there was a significant correlation between the IM trough concentration and clinical responses, especially MMR and CCyR, in CML patients. Furthermore, we found that the probability of successful treatment was correlated with the ABCG2 C421A polymorphism, at least within the Asian population. We failed to determine an association between ABCB1 polymorphisms and IM response, although the G2677T/A polymorphism might be involved. However, further large-scale investigations using more sensitive genotyping methods would be required to confirm this.- Published
- 2017
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21. Correlation between MDR1 methylation status in the promoter region and MDR1 genetic polymorphism in 194 healthy Chinese Han subjects.
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Jiang ZP, Xu P, Liu RR, Li HD, Wang GP, Zhao XL, and Chen FP
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- ATP Binding Cassette Transporter, Subfamily B, ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Adult, Data Interpretation, Statistical, Epigenesis, Genetic, Female, Genotype, Haplotypes, Humans, Male, Young Adult, ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Asian People genetics, DNA Methylation, Polymorphism, Single Nucleotide, Promoter Regions, Genetic
- Abstract
Aims: To investigate the correlation between the methylation status in the MDR1 promoter region and the MDR1 genetic polymorphism., Methods: A total of 194 unrelated subjects (105 men and 89 women) with a median age of 26 years were enrolled in this study. DNA was extracted and PCR-RFLP was performed for C1236T, C3435T and G2677T/A polymorphism genotyping. The combined bisulfite restriction analysis (COBRA) method was also performed to determine DNA methylation levels in the MDR1 promoter region. Genotype frequencies for the variants SNPs were assessed for deviation from Hardy-Weinberg equilibrium using the chi2 test. Nonparametric tests including Kruskal-Wallis method and the Mann-Whitney U test were used to compare the DNA methylation levels between different genotypes., Results: The allelic frequency distribution of the C1236T, C3435T and G2677T/A was found to be in good agreement with previous reports. Our study revealed significant correlation between different genotypes of C3435T and G2677T/A, but there is no significant difference between the different genotypes of C1236T., Conclusion: A correlation between MDR1 genetic polymorphisms C3435T and G2677T/A, as well as haplotypes derived from C1236T, G2677T/A and C3435T, with methylation status of MDR1 promoter region was found in this study. Further investigations are needed to explore the molecular mechanism and clinical significance of this correlation.
- Published
- 2008
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