"1"^^ . . . "Neuvedeno."@en . "The cryptic translocation t(12;21)(pl3;q22), leading to the juxtaposition of TEL gene from chromosome 12 to the AML1 gene on chromosome 21 is the most frequent genetic aberration in childhood acute lymphoblastic leukaemia (- 25%). Both of the transcription factors, TEL and AML1, are essential for normal haematopoiesis. TEL part of chimeric protein shares domains interacting with corepressors mSin3A, N-CoR and HDCA-3, and AML1 part contains Runt-1 DNA-binding domain which mediates interaction with DNA regulatory elements of AML1-responding genes. In TEL/AML1-positive cells, TEL fused to AML1 converts transcription activator AML1 into transcriptional repressor and thus mediates leukaemogenesis. In the current project, we aim for influencing ofTEL/AML1 function by introduction of a novel method - RNA interference (RNAi). We will test possibilities of this approach and biological properties of TEL/AML1-positive leukaemic cells knocked-down by RNAi. Alternatively, we will utilise another"@en . "0"^^ . . . "Kryptick\u00E1 translokace t(12;21) vych\u00E1zej\u00EDc\u00ED z fuse genu TEL na chromosomu 12 a genu AML1 z chromosomu 21 je nej\u010Dast\u011Bj\u0161\u00ED nen\u00E1hodnou genetickou aberac\u00ED u d\u011Btsk\u00FDch ALL (-25%). Oba partnersk\u00E9 geny jsou d\u016Fle\u017Eit\u00E9 p\u0159i v\u00FDvoji a udr\u017Een\u00ED norm\u00E1ln\u00ED hematopoesy .TEL oblast fusn\u00EDho proteinu obsahuje oblasti interaguj\u00EDc\u00ED s korepresory mSin3, N-CoR a HDAC-3. \u010C\u00E1st AML1 genu obsa\u017Een\u00E1 ve fusi obsahuje DNA v\u00E1\u017E\u00EDc\u00ED dom\u00E9nu, kter\u00E1 \u0159\u00EDd\u00ED interakci s regula\u010Dn\u00EDmi elementy genu. V TEL/AML1 positivn\u00EDch bu\u0148k\u00E1ch m\u011Bn\u00ED p\u0159\u00EDtomnost \u010D\u00E1sti genu TEL ve fusi funkci AML1 z aktiv\u00E1toru na transkrip\u010Dn\u00ED represor a tak p\u0159isp\u00EDv\u00E1 k leukemogenesi. V navrhovan\u00E9m projektu se budeme sna\u017Eit ovlivnit expresi TEL/AML1 pomoc\u00ED nov\u00E9ho postupu - RNA interference (RNAi). Budeme ov\u011B\u0159ovat mo\u017Enosti t\u00E9to metody a sledovat zm\u011Bny biologick\u00FDch vlastnost\u00ED TEL/AML1 positivn\u00EDch bun\u011Bk. Sou\u010Dasn\u011B budeme in vitro testovat mo\u017Enosti vyu\u017Eit\u00ED inhibitor\u016F HDAC k funk\u010Dn\u00EDmu ovlivn\u011Bn\u00ED efektu proteinu TEL/AML1."@cs . . . . "1"^^ . . "695"^^ . . . "695"^^ . "1"^^ . "Vliv potla\u010Den\u00ED exprese fusn\u00EDho genu TEL/AML1 pomoc\u00ED RNAi a HDACi na biologii leukemick\u00FDch blast\u016F"@cs . "0"^^ . . "Influence of inhibition of TEL/AML1 expression and function using RNAi and HDACi on leukaemic blast biology"@en .