Linked Life Data

12200696

Source:http://linkedlifedata.com/resource/pubmed/id/12200696

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2002-8-29
pubmed:abstractText
Methylthioadenosine phosphorylase (MTAP) is an important enzyme used for the salvage of adenine and methionine. Cells lacking this enzyme are expected to be sensitive to purine synthesis inhibitors and/or methionine starvation. We reported previously that the MTAP gene is deleted in adult T cell leukemia (ATL) cells. In the present study, we expanded our series and used a real-time quantitative PCR assay for accurate diagnosis of the deletion and nine of 65 primary ATL samples (13.8%) were MTAP negative. In spite of this low incidence, ATL cells showed significantly higher sensitivity to L-alanosine, an inhibitor of de novo adenosine monophosphate (AMP) synthesis, than normal lymphocytes, suggesting that the MTAP gene is inactivated not only by deletion but also by other mechanisms. Indeed, a real-time quantitative RT-PCR assay disclosed that primary ATL cells had significantly lower MTAP mRNA expression than normal lymphocytes. Since MTAP-negative ATL cell lines also showed much higher sensitivity to L-alanosine than MTAP-positive ATL cell lines, we used these cell lines to investigate whether it is possible to develop selective therapy targeting MTAP deficiency. A substrate of MTAP, methylthioadenosine (MTA) or its substitutes rescued concanavalin A (Con A)-activated normal lymphocyte proliferation from L-alanosine toxicity. All the compounds except 5'-deoxyadenosine, however, also caused the undesirable rescue of MTAP-negative ATL cell lines. 5'-Deoxyadenosine had the desired ability to rescue hematopoietic progenitor cells without rescuing ATL cell lines. These results support the rationale for a chemotherapy regimen of L-alanosine combined with 5'-deoxyadenosine rescue in MTAP-deficient ATL.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0887-6924
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1799-807
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12200696-Adenosine Monophosphate, pubmed-meshheading:12200696-Antibiotics, Antineoplastic, pubmed-meshheading:12200696-Blotting, Southern, pubmed-meshheading:12200696-Cell Division, pubmed-meshheading:12200696-Colony-Forming Units Assay, pubmed-meshheading:12200696-DNA Primers, pubmed-meshheading:12200696-Drug Resistance, Neoplasm, pubmed-meshheading:12200696-Gene Deletion, pubmed-meshheading:12200696-Humans, pubmed-meshheading:12200696-Leukemia-Lymphoma, Adult T-Cell, pubmed-meshheading:12200696-Lymphocyte Activation, pubmed-meshheading:12200696-Purine-Nucleoside Phosphorylase, pubmed-meshheading:12200696-RNA, Messenger, pubmed-meshheading:12200696-RNA, Neoplasm, pubmed-meshheading:12200696-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:12200696-Thymidine
pubmed:year
2002
pubmed:articleTitle
Chemotherapy targeting methylthioadenosine phosphorylase (MTAP) deficiency in adult T cell leukemia (ATL).
pubmed:affiliation
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't