Childhood Leukemias: Acute lymphoblastic leukemia

The uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) are key enzymes in human detoxication of xeno- and endobiotics. Potentially toxic endogenous compounds such as bilirubin, or exogenous compounds such as drugs, pesticides, and carcinogens, are generally transformed into water-soluble glucuronides for excretion in bile and urine. The UGTs are encoded by a multigene family in humans. A relatively small number of human enzymes catalyze the glucuronidation of thousands of compounds. Genetic variations and single nucleotide polymorphisms (SNPs) within the UGT genes are remarkably common, and lead to genetic polymorphisms. The multiplicity of transferases, some exhibiting overlapping substrate specificity, may provide functional compensation for genetic deficit in some cases. Genetic variation may cause different phenotypes by affecting expression levels or activities of individual UGTs. This inter-individual variation in UGTs has resulted in functional deficit affecting endogenous metabolism and leading to jaundice and other diseases. Disruption of the normal metabolic physiology, by the reduction of bile acid excretion or steroid glucuronidation, may lead to cholestasis and organ dysfunction. Deficient glucuronidation of drugs and xenobiotics have an important pharmacological impact, which may lead to drug-induced adverse reactions, and even cancer. Additional novel polymorphisms in this gene family are yet to be revealed and studied, but will have a profound effect on the development of new drugs and therapies.

Genetic variation of human UDP-glucuronosyltransferase: implications in disease and drug glucuronidation.

Role of pharmacogenomics and pharmacodynamics in the treatment of acute lymphoblastic leukaemia.

Present day paediatric co-operative group acute lymphoblastic leukaemia (ALL) protocols cure approximately 80% of patients, a result achieved largely through the use of risk-stratified therapies that employ multiple chemotherapy agents. These risk-based therapies utilize host and leukaemia traits to select the most appropriate therapy. However, these risk-stratified approaches predict therapy response imperfectly and an important fraction of patients experience relapse or therapy-related toxicity. Pharmacogenetics, the study of genetic variations in drug-processing genes and individual responses to drugs, may enable the improved identification of patients at higher risk for either disease relapse or chemotherapy-associated side effects. While the impact of genetic variation in the thiopurine-S-methyltransferase gene on ALL treatment outcome and toxicity has been extensively studied, the role of other polymorphisms remains less well known. This review summarizes current research on the impact of genetic variation in drug-processing genes in paediatric ALL and reviews important methodological and statistical issues presently challenging the field of pharmacogenetics.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2141.2004.04932.x

Pharmacogenetic determinants of outcome in acute lymphoblastic leukaemia.

Comparison of three methods for genotyping the UGT1A1 (TA)n repeat polymorphism.

Chemotherapy for malignant neoplasms sometimes causes unconjugated hyperbilirubinemia in the absence of liver dysfunction. We analyzed the association of chemotherapy-induced hyperbilirubinemia with mutations of the bilirubin uridine-5'-diphosphate (UDP)-glucuronosyltransferase gene (UGT1A1) from two leukemic patients in whom chemotherapy resulted in a hyperbilirubinemic response. We isolated genomic DNA from peripheral blood samples and amplified UGT1A1 by polymerase chain reaction. The amplified DNA fragments were analyzed by direct sequencing. The genes of the two patients revealed an identical heterozygous missense mutation in exon 1 (211G-->A: G71R). This UGT1A1 mutation may be the basis of chemotherapy-induced unconjugated hyperbilirubinemia.

Chemotherapy-induced unconjugated hyperbilirubinemia caused by a mutation of the bilirubin uridine-5'-diphosphate-glucuronosyltransferase gene.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Shigeru Ota

Author Tools

Chat about Author

Papers

Chemotherapy-induced unconjugated hyperbilirubinemia caused by a mutation of the bilirubin uridine-5'-diphosphate-glucuronosyltransferase gene.