Linked Life Data

15687366

Source:http://linkedlifedata.com/resource/pubmed/id/15687366

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-2-2
pubmed:abstractText
Down syndrome children with acute megakaryocytic leukemia (AMkL) have higher cure rates than non-Down syndrome acute myeloid leukemia (AML) patients treated with cytosine arabinoside (ara-C). Megakaryoblasts from Down syndrome AML patients are more sensitive in vitro to ara-C than cells from non-Down syndrome AML patients. Somatic mutations in the GATA1 transcription factor have been detected exclusively and almost uniformly in Down syndrome AMkL patients, suggesting a potential linkage to the chemotherapy sensitivity of Down syndrome megakaryoblasts. Stable transfection of wild-type GATA1 cDNA into the Down syndrome AMkL cell line CMK resulted in decreased (8- to 17-fold) ara-C sensitivity and a threefold-lower generation of the active ara-C metabolite ara-CTP compared with that for mock-transfected CMK cells. High intracellular levels of uridine arabinoside (ara-U) (an inactive ara-C catabolite generated by cytidine deaminase) and cytidine deaminase transcripts were detected in GATA1-transfected CMK sublines, whereas no ara-U was detected in mock-transfected cells. Cytidine deaminase transcripts were a median 5.1-fold (P = .002) lower in Down syndrome megakaryoblasts (n = 16) than in blast cells from non-Down syndrome patients (n = 56). These results suggest that GATA1 transcriptionally upregulates cytidine deaminase and that the presence or absence of GATA1 mutations in AML blasts likely confers differences in ara-C sensitivities due to effects on cytidine deaminase gene expression, which, in turn, contributes to the high cure rate of Down syndrome AMkL patients.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1460-2105
pubmed:author
pubmed:issnType
Electronic
pubmed:day
2
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
226-31
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15687366-Antimetabolites, Antineoplastic, pubmed-meshheading:15687366-Arabinofuranosylcytosine Triphosphate, pubmed-meshheading:15687366-Arabinofuranosyluracil, pubmed-meshheading:15687366-Blotting, Western, pubmed-meshheading:15687366-Child, pubmed-meshheading:15687366-Cytarabine, pubmed-meshheading:15687366-Cytidine Deaminase, pubmed-meshheading:15687366-DNA-Binding Proteins, pubmed-meshheading:15687366-Down Syndrome, pubmed-meshheading:15687366-Erythroid-Specific DNA-Binding Factors, pubmed-meshheading:15687366-GATA1 Transcription Factor, pubmed-meshheading:15687366-Humans, pubmed-meshheading:15687366-Leukemia, Megakaryoblastic, Acute, pubmed-meshheading:15687366-Polymerase Chain Reaction, pubmed-meshheading:15687366-Time Factors, pubmed-meshheading:15687366-Transcription, Genetic, pubmed-meshheading:15687366-Transcription Factors, pubmed-meshheading:15687366-Transcriptional Activation, pubmed-meshheading:15687366-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
GATA1, cytidine deaminase, and the high cure rate of Down syndrome children with acute megakaryocytic leukemia.
pubmed:affiliation
Experimental and Clinical Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't