Implementation of Pharmacogenetics to Individualize Treatment Regimens for Children with Acute Lymphoblastic Leukemia.
TL;DR: This review presents 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.
read more
Abstract: 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.
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
Neurotoxicity Associated with Treatment of Acute Lymphoblastic Leukemia Chemotherapy and Immunotherapy
TL;DR: An analysis of the current knowledge on the mechanisms of neurotoxicity of standard chemotherapy and the targeted therapy in children with ALL is presented.
19
The Relevance of Telomerase and Telomere-Associated Proteins in B-Acute Lymphoblastic Leukemia
Tales Henrique Andrade da Mota,Ricardo Camargo,Estefânia Biojone,Ana Flávia Reis Guimarães,Fabio Pittella-Silva,Diêgo Madureira de Oliveira +5 more
TL;DR: In this article , the authors highlight the biological and clinical relevance of telomerase for B-ALL and the implications of its canonical and non-canonical action on signaling pathways in the context of disease and treatment.
Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia
Clara Vicente-Garcés,Elena Esperanza-Cebollada,Sara Montesdeoca,Montserrat Torrebadell,S. Rives,José Luis Dapena,Albert Català,Nuria Conde,Mireia Camós,Nerea Vega-García +9 more
TL;DR: This work validated a reliable and reproducible method to refine pediatric AL diagnosis, prognosis, and treatment, and demonstrated the feasibility of incorporating a targeted NGS panel into pediatric hematology practice.
8
A GRIN3A polymorphism may be associated with glucocorticoid-induced symptomatic osteonecrosis in children with acute lymphoblastic leukemia.
TL;DR: In this paper, the authors evaluated the association between candidate genetic polymorphisms and glucocorticoid-induced osteonecrosis in Arab children treated for acute lymphoblastic leukemia.
3
Pharmacogenetics of pediatric acute lymphoblastic leukemia in Uruguay: adverse events related to induction phase drugs
Gabriela Burgueño-Rodríguez,Y. Méndez,N. Olano,Magdalena Schelotto,Luis Castillo,Ana María Soler,Julio da Luz +6 more
TL;DR: The importance of knowing individual genetics to improve the efficacy and safety of acute lymphoblastic leukemia is shown, as mucositis, Cushing syndrome, and neurotoxicity were the only adverse effects linked with genetic variants and ancestry.
2
References
Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia
Seth E. Karol,Leonard A. Mattano,Wenjian Yang,Kelly W. Maloney,Colton Smith,Chengcheng Liu,Laura B. Ramsey,Christian A. Fernandez,Tamara Chang,Geoffrey Neale,Cheng Cheng,Elaine R. Mardis,Robert S. Fulton,Paul Scheet,F. Anthony San Lucas,Eric C. Larsen,Mignon L. Loh,Elizabeth A. Raetz,Stephen P. Hunger,Meenakshi Devidas,Mary V. Relling +20 more
TL;DR: Top replicated SNPs were enriched in enhancers active in mesenchymal stem cells, and analysis of annotated genes demonstrated enrichment in glutamate receptor and adipogenesis pathways, which may provide new insights into the pathophysiology of osteonecrosis.
65
Mechanisms of extramedullary relapse in acute lymphoblastic leukemia: Reconciling biological concepts and clinical issues.
Jérémie Gaudichon,Hélène Jakobczyk,Lydie Debaize,Elie Cousin,Marie-Dominique Galibert,Marie-Bérengère Troadec,Virginie Gandemer +6 more
TL;DR: This review has attempted to assemble the evidence concerning the microenvironmental factors that could explain why ALL cells reside in extramedullary leukemia niches and solid tumor metastatic niches, and concludes with several examples of potential niche-based therapies which could be successfully added to current treatments of ALL.
65
Pharmacogenetics influence treatment efficacy in childhood acute lymphoblastic leukemia.
TL;DR: Beyond the thiopurine methyltransferase polymorphisms, the candidate-gene approach has not established clear associations between polymorphisms and treatment response, and high-throughput, low-cost, genetic platforms will allow screening of hundreds or thousands of targeted SNPs to give a combined gene-dosage effect (=individual SNP risk profile), which may allow pharmacogenetic-based individualization of treatment.
64
Cell Cycle Regulation by Alternative Polyadenylation of CCND1.
TL;DR: Results indicate that PAS editing with CRISPR/Cas9 provides a good method by which to study the biological function of APA, but UTR-APA and CR- APA act via different molecular mechanisms.
Lack of association of the CEP72 rs924607 TT genotype with vincristine-related peripheral neuropathy during the early phase of pediatric acute lymphoblastic leukemia treatment in a Spanish population
Angela Gutierrez-Camino,Idoia Martin-Guerrero,Elixabet Lopez-Lopez,Aizpea Echebarria-Barona,Iñaki Zabalza,Irune Ruiz,Isabel Guerra-Merino,Africa Garcia-Orad +7 more
TL;DR: Whether the CEP72 rs924607 TT genotype is a useful marker of vincristine neuropathy during induction therapy among Spanish children with B-ALL treated on the LAL-SHOP protocols is determined.
61