Genetic Risk Factors for VIPN in Childhood Acute Lymphoblastic Leukemia Patients Identified Using Whole-Exome Sequencing

Abaji, Rachid; Ceppi, Francesco; Patel, Swati; Gagné, Vincent; Xu, Chang; Spinella, Jean-François; Colombini, Antonella; Parasole, Rosanna; Buldini, Barbara; Basso, Giuseppe; Conter, Valentino; Cazzaniga, Giovanni; Leclerc, Jean‐Marie; Laverdière, Caroline; Sinnett, Daniel; Krajinović, Maja

doi:10.2217/pgs-2018-0093

Cited by 27 publications

(44 citation statements)

References 53 publications

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“…Also several haplotypes were associated with neurotoxicity. Abaji et al (2018) screened retrospectively WES data of ALL patients to find possible new gene variants which could be associated with VIPN. In this study, three new gene variants are association with VIPN: Spectrin Repeat Containing Nuclear Envelope Protein 2 (SYNE2) (rs2781377), Mitochondrial Ribosomal Protein L47 (MRPL47) (rs10513762) and Bromo Adjacent Homology Domain Containing 1 (BAHD1) (rs3803357).…”

Section: Pharmacodynamics Stability Of Microtubules and Neurotoxicitmentioning

confidence: 99%

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Pharmacogenomics as a Tool to Limit Acute and Long-Term Adverse Effects of Chemotherapeutics: An Update in Pediatric Oncology

et al. 2020

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Section: Pharmacodynamics Stability Of Microtubules and Neurotoxicitmentioning

confidence: 99%

“… Abaji et al. (2018) screened retrospectively WES data of ALL patients to find possible new gene variants which could be associated with VIPN.…”

Section: Role Of Pharmacogenetic Variations In Chemotherapeutic Relatmentioning

confidence: 99%

Pharmacogenomics as a Tool to Limit Acute and Long-Term Adverse Effects of Chemotherapeutics: An Update in Pediatric Oncology

et al. 2020

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“…In a cohort of 237 children with ALL, Abaji et al 66 identified 2 genetic polymorphisms that put patients receiving chemotherapy at risk for peripheral neurotoxicity. The first polymorphism is rs2781377 in spectrin repeat-containing nuclear envelope protein 2 (SYNE2) , which codes for nesprin, a nuclear envelope spectrin repeat protein that maintains cellular cytoskeleton.…”

Section: Variants Associated With All Treatment Toxicitiesmentioning

confidence: 99%

“… 74 , 161 Results were however not replicated in two other studies. 162 , 163 More recently whole-exome sequencing of DNA from 240 European children with ALL revealed an association between four variants in four genes ( BAHD1 rs3803357, MRPL47 rs10513762, SYNE2 rs2781377 , and CDH2 rs1944294 ) with VINC-related neuropathy, 66 however these results were not yet validated in other populations.…”

Section: Evidence For the Individualization Of Treatment Regimensmentioning

confidence: 99%

<p>Implementation of Pharmacogenetics to Individualize Treatment Regimens for Children with Acute Lymphoblastic Leukemia</p>

Maamari

El-Khoury

Saifi

et al. 2020

PGPM

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Despite major advances in the management and high cure rates of childhood acute lymphoblastic leukemia (ALL), patients still suffer from many drug-induced toxicities, sometimes necessitating dose reduction, or halting of cytotoxic drugs with a secondary risk of disease relapse. In addition, investigators have noted significant inter-individual variability in drug toxicities and disease outcomes, hence the role of pharmacogenetics (PGx) in elucidating genetic polymorphisms in candidate genes for the optimization of disease management. In this review, we present the PGx data in association with main toxicities seen in children treated for ALL in addition to efficacy, with a focus on the most plausible germline PGx variants. We then follow with a summary of the highest evidence drug-gene annotations with suggestions to move forward in implementing preemptive PGx for the individualization of treatment regimens for children with ALL.

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“…Recently, a whole-exome sequencing analysis combined with an exome-wide association study was performed to find out genetic risk factors for VCR-related neurotoxicity [64]. The study identified two variants significantly associated with an increased risk of high-grade VCR-related neurotoxicity, rs2781377 in the SYNE2 gene and rs10513762 in the MRPL47 gene.…”

Section: Vincristinementioning

confidence: 99%

Pharmacogenomic and Pharmacotranscriptomic Profiling of Childhood Acute Lymphoblastic Leukemia: Paving the Way to Personalized Treatment

Pavlović

Kotur

Stanković

et al. 2019

Genes

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Personalized medicine is focused on research disciplines which contribute to the individualization of therapy, like pharmacogenomics and pharmacotranscriptomics. Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. It is one of the pediatric malignancies with the highest cure rate, but still a lethal outcome due to therapy accounts for 1%–3% of deaths. Further improvement of treatment protocols is needed through the implementation of pharmacogenomics and pharmacotranscriptomics. Emerging high-throughput technologies, including microarrays and next-generation sequencing, have provided an enormous amount of molecular data with the potential to be implemented in childhood ALL treatment protocols. In the current review, we summarized the contribution of these novel technologies to the pharmacogenomics and pharmacotranscriptomics of childhood ALL. We have presented data on molecular markers responsible for the efficacy, side effects, and toxicity of the drugs commonly used for childhood ALL treatment, i.e., glucocorticoids, vincristine, asparaginase, anthracyclines, thiopurines, and methotrexate. Big data was generated using high-throughput technologies, but their implementation in clinical practice is poor. Research efforts should be focused on data analysis and designing prediction models using machine learning algorithms. Bioinformatics tools and the implementation of artificial i Lack of association of the CEP72 rs924607 TT genotype with intelligence are expected to open the door wide for personalized medicine in the clinical practice of childhood ALL.

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Genetic Risk Factors for VIPN in Childhood Acute Lymphoblastic Leukemia Patients Identified Using Whole-Exome Sequencing

Abstract: Variants in SYNE2, MRPL47 and BAHD1 genes are putative new risk factors for VIPN in childhood acute lymphoblastic leukemia.

Cited by 27 publications

References 53 publications

Pharmacogenomics as a Tool to Limit Acute and Long-Term Adverse Effects of Chemotherapeutics: An Update in Pediatric Oncology

Pharmacogenomics as a Tool to Limit Acute and Long-Term Adverse Effects of Chemotherapeutics: An Update in Pediatric Oncology

<p>Implementation of Pharmacogenetics to Individualize Treatment Regimens for Children with Acute Lymphoblastic Leukemia</p>

Pharmacogenomic and Pharmacotranscriptomic Profiling of Childhood Acute Lymphoblastic Leukemia: Paving the Way to Personalized Treatment

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