MicroRNAs Mediated Regulation of Expression of Nucleoside Analog Pathway Genes in Acute Myeloid Leukemia

Bhise, Neha; Elsayed, Abdelrahman H.; Cao, Xueyuan; Pounds, Stanley; Lamba, Jatinder K.

doi:10.3390/genes10040319

Cited by 7 publications

(8 citation statements)

References 31 publications

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“…It is necessary to define the optimal approach to implement clinical testing in diverse health care practices, including the timing and methodology of genotyping in clinical settings. 43 Furthermore, for chronic therapy (ie, >12 weeks) in patients who are classified as having the CYP2C19 PM phenotype, a reduction in the daily dose by 50% is recommended due to an increase in the plasma concentration of PPI and the chance of potential toxicity compared to those who are classified as having the NM phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…In the future, the use of a panel-based preventive approach before prescribing medications will require genotype information on hundreds of pharmacogenes readily available in the patient’s medical history to guide drug therapy. 43 In our population, it is necessary to determine the frequency of the polymorphisms in these pharmacogenes previously reported in the literature before implementing these approaches. This will elucidate the impact of a polymorphism on the metabolizing phenotype and even decrease the influence of other genetic or nongenetic factors, since a correct genotype and metabolizer phenotype correlation was not possible in all patients.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of CYP2C19 Gene Polymorphisms in Patients with Acid Peptic Disorders Treated with Esomeprazole

Díaz-Ordóñez¹,

Ramírez‐Montaño²,

Candelo³

et al. 2021

PGPM

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Background CYP2C19 is a highly polymorphic gene that encodes an enzyme with the same name and whose function is associated with the metabolism of many important drugs, such as proton pump inhibitors (such as esomeprazole, which is used for the treatment of acid peptic disease). Genetic variants in CYP2C19 alter protein function and affect drug metabolism. This study aims to genotypically and phenotypically characterize the genetic variants in the CYP2C19 gene in 12 patients with acid peptic disorders and different therapeutic profiles to proton pump inhibitor (PPI) drugs. The patients were randomly selected from a controlled, randomized and blinded clinical pilot trial of 33 patients. We determined the presence and frequency of single nucleotide polymorphisms (SNPs) within exons 1–5 and 9, the intron-exon junctions, and a fragment in the 3ʹ UTR region of the CYP2C19 gene using Sanger sequencing. Undescribed polymorphisms were analyzed by free online bioinformatics tools to evaluate the potential molecular effects of these genetic variants. Results We identified nine polymorphisms, six of which had no reported functions. One of these genetic variants, with a functional impact, not yet reported (p.Arg132Trp) was predicted by bioinformatic tools as potentially pathogenic. This finding suggests that p.Arg132Trp could be related to poor metabolizers of drugs metabolized by CYP2C19. Conclusion We identified the genotype spectrum of variants in CYP2C19 . The genotype spectrum of variants in CYP2C19 could predict the treatment response and could support to evaluate clinical efficacy in patients treated with esomeprazole.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of CYP2C19 Gene Polymorphisms in Patients with Acid Peptic Disorders Treated with Esomeprazole

Díaz-Ordóñez¹,

Ramírez‐Montaño²,

Candelo³

et al. 2021

PGPM

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“…It is noticed that Xu et al [ 12 ] found that miR-381 is associated with multidrug resistance in leukemia. In addition, the nucleotide analog cytarabine is a major component of AML chemotherapy, and Bhise et al [ 8 ] identified miRNAs that were significantly associated with nucleotide pathway gene expression in multiple AML cell lines, including miR-381. Therefore, we speculate that miR-381 may play an important role in pediatric AML.…”

Section: Discussionmentioning

confidence: 99%

“…What is interesting is that the nucleic acid analog cytarabine is a major component of chemotherapy for AML. Bhise et al [ 8 ] identified miRNAs involved in the regulation of mRNA expression levels of cytosine arabinoside pathway genes in multiple AML cell lines, including miR-381. miR-381 is located on the human chromosome 14q32.31 and has been reported to be involved in the progression of tumors, including gastric cancer, breast cancer, and colorectal cancer [ 9 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of dysregulation of miR-381 in pediatric acute myeloid leukemia

Zhang

Sun

et al. 2020

Eur J Med Res

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Background microRNA-381 is dysregulated in a variety of cancers. However, its clinical significance in pediatric acute myeloid leukemia (AML) is still unclear. The purpose of this study was to detect the expression level of miR-381 in pediatric AML patients and to explore its potential clinical significance. Methods The levels of miR-381 in bone marrow and serum of 102 pediatric AML patients were measured by quantitative real-time polymorperase chain reaction (qRT-PCR). The diagnostic value of serum miR-381 in pediatric AML patients was evaluated by the receiver operating characteristic (ROC) curve. A Chi square test was used to analyze the relationship between serum miR-381 and the clinical characteristics of patients. Cox regression analysis and Kaplan–Meier evaluated the prognostic value of serum miR-381 in patients. Finally, the proliferation of the cells was analyzed by the CCK-8 assay. Results Compared with healthy controls, the levels of miR-381 in serum and bone marrow of pediatric AML patients were significantly decreased (P < 0.001). ROC curve showed that miR-381 could distinguish pediatric AML cases from normal controls. At the same time, the downregulation of miR-381 was associated with M7 in the French–American–British (FAB) classifications and unfavorable cytogenetic risks (P < 0.05). Low serum miR-381 levels were associated with poor overall survival of pediatric AML (log-rank test, P = 0.011) and poor relapse-free survival (log-rank test, P = 0.004). Cox regression analysis confirmed that reduced serum miR-381 was an independent predictor of poor prognosis in AML (HR = 3.794, 95% CI 1.3633–10.559, P = 0.011). In addition, low expression of miR-381 significantly reduced the proliferation of cells (P < 0.05). Conclusion All experimental results confirm that miR-381 has reduced bone marrow and serum expression in pediatric AML, and low levels of serum miR-381 have certain diagnostic and prognostic value in pediatric AML and may be a potential therapeutic target for AML.

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“…The effect on azathioprine metabolite concentration and dose was confirmed for GST-M1 and TPMT . Bise and colleagues [ 9 ] evaluate the potential involvement of miRNAs in determining the variation in expression levels of drug transporters or enzymes involved in the activation or inactivation of cytarabine and other analogs, an important mechanism potentially determining drug resistance. The authors evaluate miRNA and gene-expression levels of cytarabine metabolic pathway genes in 8 AML cell lines and the TCGA database, demonstrating that miR-34a-5p and miR-24-3p regulate DCK, an enzyme involved in activation of cytarabine, and DCTD, an enzyme involved in metabolic inactivation of cytarabine expression, respectively.…”

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confidence: 99%

Pharmacogenomics and Personalized Medicine

Cecchin

Stocco

2020

Genes

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Pharmacogenomics is one of the emerging approaches to precision medicine, tailoring drug selection and dosing to the patient’s genetic features. In recent years, several pharmacogenetic guidelines have been published by international scientific consortia, but the uptake in clinical practice is still poor. Many coordinated international efforts are ongoing in order to overcome the existing barriers to pharmacogenomic implementation. On the other hand, existing validated pharmacogenomic markers can explain only a minor part of the observed clinical variability in the therapeutic outcome. New investigational approaches are warranted, including the study of the pharmacogenomic role of the immune system genetics and of previously neglected rare genetic variants, reported to account for a large part of the inter-individual variability in drug metabolism. In this Special Issue, we collected a series of articles covering many aspects of pharmacogenomics. These include clinical implementation of pharmacogenomics in clinical practice, development of tools or infrastractures to support this process, research of new pharmacogenomics markers to increase drug efficacy and safety, and the impact of rare genetic variants in pharmacogenomics.

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MicroRNAs Mediated Regulation of Expression of Nucleoside Analog Pathway Genes in Acute Myeloid Leukemia

Cited by 7 publications

References 31 publications

Evaluation of CYP2C19 Gene Polymorphisms in Patients with Acid Peptic Disorders Treated with Esomeprazole

Evaluation of CYP2C19 Gene Polymorphisms in Patients with Acid Peptic Disorders Treated with Esomeprazole

Clinical significance of dysregulation of miR-381 in pediatric acute myeloid leukemia

Pharmacogenomics and Personalized Medicine

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