کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8733615 1590691 2018 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Genomics and pharmacogenomics of pediatric acute lymphoblastic leukemia
ترجمه فارسی عنوان
ژنومیک و فارماکولوژی زایی از لوسمی لنفوبلاستی حاد کودکان
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی هماتولوژی
چکیده انگلیسی
Acute lymphoblastic leukaemia (ALL) is a prevalent form of pediatric cancer that accounts for 70-80% of all leukemias. Genome-based analysis, exome sequencing, transcriptomics and proteomics have provided insight into genetic classification of ALL and helped identify novel subtypes of the disease. B and T cell-based ALL are two well-characterized genomic subtypes, significantly marked by bone marrow disorders, along with mutations in trisomy 21 and T53. The other ALLs include Early T-cell precursor ALL, Philadelphia chromosome-like ALL, Down syndrome-associated ALL and Relapsed ALL. Chromosomal number forms a basis of classification, such as, hypodiploid ALL, near-haploid, low-hypodiploid, high-hypodiploid and hypodiploid-ALL. Advances in therapies targeting ALL have been noteworthy, with significant pre-clinical and clinical studies on drug pharmacokinetics and pharmacodynamics. Methotrexate and 6-mercaptopurine are leading drugs with best demonstrated efficacies against childhood ALL. The drugs in combination, following dose titration, have also been used for maintenance therapy. Methotrexate-polyglutamate is a key metabolite that specifically targets the disease pathogenesis, and 6-thioguanine nucleotides, derived from 6-mercaptopurine, impede replication and transcription processes, inducing cytotoxicity. Additionally, glucocorticoids, asparaginase, anthracycline, vincristine and cytarabine that trans-repress gene expression, deprives cells of asparagine, triggers cell cycle arrest, influences cytochrome-P450 polymorphism and inhibits DNA polymerase, respectively, have been used in chemotherapy in ALL patients. Overall, this review covers the progress in genome technology related to different sub-types of ALL and pharmacokinetics and pharmacodynamics of its medications. It also enlightens adverse effects of current drugs, and emphasizes the necessity of genome-wide association studies for restricting childhood ALL.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Critical Reviews in Oncology/Hematology - Volume 126, June 2018, Pages 100-111
نویسندگان
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