Genomics and pharmacogenomics of pediatric acute lymphoblastic leukemia

Critical Reviews in Oncology/hematology
Chuan Wu, Wei Li

Abstract

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-mer...Continue Reading

Citations

Jan 7, 2020·Journal of Cellular Physiology·Cecilia EvangelistiCamilla Evangelisti
Jun 26, 2020·Communications Biology·Tamara RothenburgerJindrich Cinatl
Jan 11, 2020·Frontiers in Oncology·Antonello Di PaoloSara Galimberti
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Jan 26, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Ricardo Ballesteros-RamírezSusana Fiorentino
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