The influence of polymorphisms in the drug transporter, ABCB1 on the toxicity of glucocorticoids in Saudi children with acute lymphoblastic leukaemia

El-Fayoumi, Refaat Ibrahim; Hagras, Magda M.; Abozenadaha, Adel; Gari, Mamdouh; Abosoudah, Ibrahim; Shinawi, Thoraia; Mirza, Talaat; Bawazir, Waleed M.

doi:10.1016/j.pharep.2018.09.010

Cited by 7 publications

(10 citation statements)

References 39 publications

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“…It is noteworthy to mention a study that was conducted on Saudi children with acute lymphoblastic leukemia, which revealed that there is no correlation between the effectiveness and safety of glucocorticoids and the rs1128503 SNP [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the Drug Transporter Gene ABCB1 Are Associated with Drug Response in Saudi Epileptic Pediatric Patients

Magadmi,

Alyoubi,

Moshrif

et al. 2023

Biomedicines

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Epilepsy is one of the most common chronic neurodisorders in the pediatric age group. Despite the availability of over 20 anti-seizure medications (ASMs) on the market, drug-resistant epilepsy still affects one-third of individuals. Consequently, this research aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of the ATP-binding cassette subfamily B member 1 (ABCB1) gene in epileptic pediatric patients and their response to ASMs. This multicentric, cross-sectional study was conducted among Saudi children with epilepsy in Jeddah, Saudi Arabia. The polymorphism variants of ABCB1 rs1128503 at exon 12, rs2032582 at exon 21, and rs1045642 at exon 26 were genotyped using the Sanger sequencing technique. The study included 85 children with epilepsy: 43 patients demonstrated a good response to ASMs, while 42 patients exhibited a poor response. The results revealed that good responders were significantly more likely to have the TT genotypes at rs1045642 and rs2032582 SNPs compared to poor responders. Additionally, haplotype analysis showed that the T-G-C haplotype at rs1128503, rs2032582, and rs1045642 was only present in poor responders. In conclusion, this study represents the first pharmacogenetic investigation of the ABCB1 gene in Saudi epileptic pediatric patients and demonstrates a significant association between rs1045642 and rs2032582 variants and patient responsiveness. Despite the small sample size, the results underscore the importance of personalized treatment for epileptic patients.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms in the Drug Transporter Gene ABCB1 Are Associated with Drug Response in Saudi Epileptic Pediatric Patients

Magadmi,

Alyoubi,

Moshrif

et al. 2023

Biomedicines

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“…Early response to GC treatment is accepted as important prognostic criteria. [25][26][27] GC response is determined by the blast count of the 8th day of the therapy. Therefore, it is crucial for better treatment of pediatric ALL to investigate, understand, and overcome the problems related to the pharmacogenomic profiles of those patients that respond poorly to initial GC treatment.…”

Section: Discussionmentioning

confidence: 99%

Genetic Profiling of Pediatric Patients with B-Cell Precursor Acute Lymphoblastic Leukemia

et al. 2022

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B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous leukemia subgroup. It has multiple sub-types that are likely to be classified by prognostic factors. Following a systematic literature review, this study analyzed the genes correlated with BCP-ALL prognosis (IKZF1, PAX5, EBF1, CREBBP, CRLF2, JAK2, ERG, CXCR4, ZAP70, VLA4, NF1, NR3C1, RB1, TSLP, ZNRF1, and FOXO3A), specifically their nucleotide variations and expression profiles in pediatric BCP-ALL samples. The study included 45 pediatric BCP-ALL patients with no cytogenetic anomaly and a control group of 10 children. The selected genes' hot-spot regions were sequenced using next-generation sequencing, while Polymorphism Phenotyping v2 and Supplemental Nutrition Assistance Program were used to identify pathogenic mutations. The expression analysis was performed using quantitative real-time polymerase chain reaction. The mutation analysis detected 328 variants (28 insertions, 47 indels, 74 nucleotide variants, 75 duplications, and 104 deletions). The most and least frequently mutated genes were IKZF1 and CREBBP, respectively. There were statistically significant differences between patients and controls for mutation distribution in eight genes (ERG, CRLF2, CREBBP, TSLP, JAK2, ZAP70, FOXO3A, and NR3C1). The expression analysis revealed that JAK and ERG were significantly overexpressed in patients compared with controls (respectively, p = 0.004 and p = 0.003). This study combined genes and pathways previously analyzed in pediatric BCP-ALL into one dataset for a comprehensive analysis from the same samples to unravel candidate prognostic biomarkers. Novel mutations were identified in all of the studied genes.

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“…Группой исследователей N.K. Zgheib et al была обнаружена значимая ассоциация между тяжелой нейтропенией (абсолютное число нейтрофилов < 500/мкл) и носительством вариантов аллелей ABCB1 rs1045642 и rs1128503 у 127 ливанских пациентов с ОЛЛ [18], а один из этих полиморфизмов -rs1045642 в ABCB1 -может быть ассоциирован с развитием потенциально опасных для жизни инфекций во время терапии ОЛЛ, как было обнаружено у 70 пациентов из Саудовской Аравии [19].…”

Section: миелотоксичностьunclassified

Genetic basis of clinical variants of chemotherapy toxicity in children with acute lymphoblastic leukemia (literature review)

Gurieva

Savelyeva

Валиев

2022

Ross. ž. det. gematol. onkol.

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Несмотря на значительные успехи в лечении и высокие показатели излечения острого лимфобластного лейкоза (ОЛЛ) у детей, пациенты все еще страдают от многочисленных нежелательных лекарственных реакций, иногда требующих снижения дозы или даже прекращения приема цитотоксических препаратов с вторичным риском рецидива заболевания. Кроме того, исследователи отмечают значительную межиндивидуальную вариабельность лекарственной токсичности и исходов заболевания, что обусловливает роль фармакогенетики (ФГ) в выявлении генетических полиморфизмов в генах-кандидатах для оптимизации лечения заболевания. По всему миру проводятся исследования, направленные на анализ корреляций между генетическими полиморфизмами и проявлениями токсичности в различных этнических группах больных. В России подобные исследования крайне редки. В данной обзорной статье мы приводим аннотации генов-кандидатов лекарств с наивысшей степенью доказательности их роли в проявлении различных клинических вариантов токсичности и предложения по дальнейшему внедрению ФГ для индивидуализации протоколов лечения детей с ОЛЛ.

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The influence of polymorphisms in the drug transporter, ABCB1 on the toxicity of glucocorticoids in Saudi children with acute lymphoblastic leukaemia

Cited by 7 publications

References 39 publications

Polymorphisms in the Drug Transporter Gene ABCB1 Are Associated with Drug Response in Saudi Epileptic Pediatric Patients

Polymorphisms in the Drug Transporter Gene ABCB1 Are Associated with Drug Response in Saudi Epileptic Pediatric Patients

Genetic Profiling of Pediatric Patients with B-Cell Precursor Acute Lymphoblastic Leukemia

Genetic basis of clinical variants of chemotherapy toxicity in children with acute lymphoblastic leukemia (literature review)

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