| pubmed-article:12200696 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12200696 | lifeskim:mentions | umls-concept:C0023493 | lld:lifeskim |
| pubmed-article:12200696 | lifeskim:mentions | umls-concept:C0013216 | lld:lifeskim |
| pubmed-article:12200696 | lifeskim:mentions | umls-concept:C0011155 | lld:lifeskim |
| pubmed-article:12200696 | lifeskim:mentions | umls-concept:C1417407 | lld:lifeskim |
| pubmed-article:12200696 | lifeskim:mentions | umls-concept:C0599894 | lld:lifeskim |
| pubmed-article:12200696 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:12200696 | pubmed:dateCreated | 2002-8-29 | lld:pubmed |
| pubmed-article:12200696 | 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. | lld:pubmed |
| pubmed-article:12200696 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12200696 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12200696 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:12200696 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12200696 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:12200696 | pubmed:issn | 0887-6924 | lld:pubmed |
| pubmed-article:12200696 | pubmed:author | pubmed-author:YamadaYY | lld:pubmed |
| pubmed-article:12200696 | pubmed:author | pubmed-author:MatsuoTT | lld:pubmed |
| pubmed-article:12200696 | pubmed:author | pubmed-author:SasakiHH | lld:pubmed |
| pubmed-article:12200696 | pubmed:author | pubmed-author:IkedaSS | lld:pubmed |
| pubmed-article:12200696 | pubmed:author | pubmed-author:TomonagaMM | lld:pubmed |
| pubmed-article:12200696 | pubmed:author | pubmed-author:SugaharaKK | lld:pubmed |
| pubmed-article:12200696 | pubmed:author | pubmed-author:KamihiraSS | lld:pubmed |
| pubmed-article:12200696 | pubmed:author | pubmed-author:HirakataYY | lld:pubmed |
| pubmed-article:12200696 | pubmed:author | pubmed-author:KudohMM | lld:pubmed |
| pubmed-article:12200696 | pubmed:author | pubmed-author:SodaHH | lld:pubmed |
| pubmed-article:12200696 | pubmed:author | pubmed-author:NoboriTT | lld:pubmed |
| pubmed-article:12200696 | pubmed:author | pubmed-author:HarasawaHH | lld:pubmed |
| pubmed-article:12200696 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12200696 | pubmed:volume | 16 | lld:pubmed |
| pubmed-article:12200696 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12200696 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12200696 | pubmed:pagination | 1799-807 | lld:pubmed |
| pubmed-article:12200696 | pubmed:dateRevised | 2007-11-15 | lld:pubmed |
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| pubmed-article:12200696 | pubmed:year | 2002 | lld:pubmed |
| pubmed-article:12200696 | pubmed:articleTitle | Chemotherapy targeting methylthioadenosine phosphorylase (MTAP) deficiency in adult T cell leukemia (ATL). | lld:pubmed |
| pubmed-article:12200696 | pubmed:affiliation | Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. | lld:pubmed |
| pubmed-article:12200696 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12200696 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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