Linked Life Data

7703493

Source:http://linkedlifedata.com/resource/pubmed/id/7703493

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1995-5-9
pubmed:abstractText
The activity of thiopurine methyltransferase (TPMT) exhibits genetic polymorphism, with approximately 1 in 300 individuals inheriting TPMT deficiency as an autosomal recessive trait, and about 11% having intermediate activity (ie, heterozygotes). Patients with TPMT deficiency accumulate excessive concentrations of 6-thioguanine nucleotides (TGNs) and develop severe toxicity when treated with standard dosages of mercaptopurine. High TPMT activity has been associated with lower concentrations of TGNs, yielding a higher risk of treatment failure in children with acute lymphoblastic leukemia (ALL). As the biochemical basis of these pharmacodynamic relationships has not been fully elucidated, we investigated the variability and relationship of TPMT activity in erythrocytes and lymphoblasts from children with ALL. A 58-fold range of erythrocyte TPMT activity was found among 119 patients receiving ALL chemotherapy (0.6 to 34.9 U/mL packed erythrocytes), but relatively low intrapatient variability (coefficient of variation, 13.5%) was observed over 1 year. A 27-fold range in TPMT activity was observed in leukemic blasts obtained from 42 patients at initial diagnosis (3.3 to 88.9 U/1 x 10(9) cells). TPMT activity in leukemic blasts at diagnosis was significantly correlated with TPMT in erythrocytes before therapy (rs = .75, P < .0001, N = 13). These data document extensive interpatient variability of TPMT activity in ALL blasts and establish its linkage to polymorphic TPMT activity in erythrocytes, providing a new mechanism by which erythrocytes serve as prognostic markers of mercaptopurine metabolism and TPMT activity in children with ALL.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1897-902
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:7703493-6-Mercaptopurine, pubmed-meshheading:7703493-Adolescent, pubmed-meshheading:7703493-Aneuploidy, pubmed-meshheading:7703493-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:7703493-Bone Marrow, pubmed-meshheading:7703493-Child, pubmed-meshheading:7703493-Child, Preschool, pubmed-meshheading:7703493-Cytarabine, pubmed-meshheading:7703493-Erythrocytes, pubmed-meshheading:7703493-Female, pubmed-meshheading:7703493-Humans, pubmed-meshheading:7703493-Lymphocytes, pubmed-meshheading:7703493-Male, pubmed-meshheading:7703493-Methotrexate, pubmed-meshheading:7703493-Methyltransferases, pubmed-meshheading:7703493-Neoplasm Proteins, pubmed-meshheading:7703493-Neoplastic Stem Cells, pubmed-meshheading:7703493-Polymorphism, Genetic, pubmed-meshheading:7703493-Precursor Cell Lymphoblastic Leukemia-Lymphoma, pubmed-meshheading:7703493-Prognosis, pubmed-meshheading:7703493-Remission Induction, pubmed-meshheading:7703493-Teniposide, pubmed-meshheading:7703493-Treatment Failure, pubmed-meshheading:7703493-Tumor Markers, Biological
pubmed:year
1995
pubmed:articleTitle
Polymorphic thiopurine methyltransferase in erythrocytes is indicative of activity in leukemic blasts from children with acute lymphoblastic leukemia.
pubmed:affiliation
Pharmaceutical Department, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't