Publication
Identification of genetic alterations occurring in pre-tcell receptor (TCR)-deficient leukemia
| dc.contributor.advisor | Santos, Nuno Rodrigues dos | |
| dc.contributor.author | Al-Dalali, Faiza Ahmed Ahmed | |
| dc.date.accessioned | 2014-04-22T14:44:43Z | |
| dc.date.available | 2014-04-22T14:44:43Z | |
| dc.date.issued | 2011 | |
| dc.description | Dissertação de mest., Ciências Biomédicas, Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2011 | por |
| dc.description.abstract | T-cell acute lymphoblastic leukemia (T-ALL) is a thymocyte malignancy. Although the identification of several genetic alterations in this leukemia has allowed a better understanding of how it develops, more research is required to develop more efficient therapies. The pre-T cell receptor (pre-TCR) complex has been characterized structurally and functionally and is an essential player in T-cell development. However, its contribution to T-cell leukemogenesis remains controversial. Indeed, reports have noticed the importance of the pre-TCR in some mouse models of T-cell leukemia. T-ALL mouse models are useful to study the cellular and molecular mechanisms underlying this disease. Regarding the TEL-JAK2 transgenic mouse model, it was found that the absence of the pre-TCR complex from T lymphocytes led to a significant delay in T-ALL onset. A genomic DNA analysis by array comparative genomic hybridization (aCGH) revealed that late-onset pre-TCR-negative leukemias presented more genomic alterations (gains and losses of DNA) than early-onset pre-TCR-positive leukemias, indicating that these alterations can occur and be selected to compensate for the absence of pre-TCR. The goal of this project was to identify genes aberrantly expressed in pre-TCR-negative leukemia. To this end, the copy number of candidate genes were compared between leukemic cells from regular TEL-JAK2 mice and TEL-JAK2 mice without the Rag2 gene, which is essential for the pre-TCR complex formation. The Cdkn2a, Cdkn2b, Myc, Ikaros, Pten, Bcl11b, and Fbxw7 genes, which are localized in genomic regions previously found to be altered in pre-TCR-deficient leukemic cells and/or are involved in cancer, have been analyzed. By performing quantitative PCR (qPCR) we found DNA copy number alterations in TEL-JAK2;Rag2-/- leukemia DNA as compared to regular TEL-JAK2 leukemia DNA in the same genomic regions that showed chromosomal abnormality in aCGH analysis. Further studies need to be performed to better understand the precise role of pre-TCR in T-ALL and the role of compensatory mechanisms occurring in the absence of pre-TCR. | por |
| dc.identifier.uri | http://hdl.handle.net/10400.1/3780 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.subject | Ciências biomédicas | por |
| dc.subject | Leucemia | por |
| dc.subject | Medula | por |
| dc.subject | Anemia | por |
| dc.subject | Quimioterapia | por |
| dc.subject | Crianças | por |
| dc.title | Identification of genetic alterations occurring in pre-tcell receptor (TCR)-deficient leukemia | por |
| dc.type | master thesis | |
| dspace.entity.type | Publication | |
| rcaap.rights | restrictedAccess | por |
| rcaap.type | masterThesis | por |
| thesis.degree.grantor | Universidade do Algarve. Faculdade de Ciências e Tecnologia | por |
| thesis.degree.level | Mestre | por |
| thesis.degree.name | Mestrado em Ciências Biomédicas | por |