| pubmed-article:18688286 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18688286 | lifeskim:mentions | umls-concept:C0017296 | lld:lifeskim |
| pubmed-article:18688286 | lifeskim:mentions | umls-concept:C0030705 | lld:lifeskim |
| pubmed-article:18688286 | lifeskim:mentions | umls-concept:C0015127 | lld:lifeskim |
| pubmed-article:18688286 | lifeskim:mentions | umls-concept:C0598766 | lld:lifeskim |
| pubmed-article:18688286 | lifeskim:mentions | umls-concept:C1314792 | lld:lifeskim |
| pubmed-article:18688286 | lifeskim:mentions | umls-concept:C0544886 | lld:lifeskim |
| pubmed-article:18688286 | lifeskim:mentions | umls-concept:C0079868 | lld:lifeskim |
| pubmed-article:18688286 | lifeskim:mentions | umls-concept:C0439661 | lld:lifeskim |
| pubmed-article:18688286 | lifeskim:mentions | umls-concept:C0205195 | lld:lifeskim |
| pubmed-article:18688286 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:18688286 | pubmed:dateCreated | 2008-9-4 | lld:pubmed |
| pubmed-article:18688286 | pubmed:abstractText | X-linked SCID (SCID-X1) is amenable to correction by gene therapy using conventional gammaretroviral vectors. Here, we describe the occurrence of clonal T cell acute lymphoblastic leukemia (T-ALL) promoted by insertional mutagenesis in a completed gene therapy trial of 10 SCID-X1 patients. Integration of the vector in an antisense orientation 35 kb upstream of the protooncogene LIM domain only 2 (LMO2) caused overexpression of LMO2 in the leukemic clone. However, leukemogenesis was likely precipitated by the acquisition of other genetic abnormalities unrelated to vector insertion, including a gain-of-function mutation in NOTCH1, deletion of the tumor suppressor gene locus cyclin-dependent kinase 2A (CDKN2A), and translocation of the TCR-beta region to the STIL-TAL1 locus. These findings highlight a general toxicity of endogenous gammaretroviral enhancer elements and also identify a combinatorial process during leukemic evolution that will be important for risk stratification and for future protocol design. | lld:pubmed |
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| pubmed-article:18688286 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18688286 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18688286 | pubmed:citationSubset | AIM | lld:pubmed |
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| pubmed-article:18688286 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18688286 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:18688286 | pubmed:issn | 0021-9738 | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:StaalFrank... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:LinchDavid... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:ThrasherAdria... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:KinnonChristi... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:GaleRosemary... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:von... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:SchmidtManfre... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:KempskiHelena... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:GilmourKimber... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:AdamsStuartS | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:HubankMichael... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:GasparH... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:AncliffPhilip... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:ParsleyKathry... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:Schwarzwaelde... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:Pike-OverzetK... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:de... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:BrugmanMartij... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:WebbDavid KDK | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:HoweSteven... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:BartholomaeCy... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:MansourMarc... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:ThornhillSusa... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:BayfordJinhua... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:ChattersSteph... | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:BrownLucieL | lld:pubmed |
| pubmed-article:18688286 | pubmed:author | pubmed-author:QuayeMichelle... | lld:pubmed |
| pubmed-article:18688286 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:18688286 | pubmed:volume | 118 | lld:pubmed |
| pubmed-article:18688286 | pubmed:owner | NLM | lld:pubmed |
