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Description
| - Translocation (12;21), the most frequent chromosomal aberration in childhood acute lymphoblastic leukemia, creates TEL/AML1 fusion gene. Resulting hybrid protein was shown to have a role in pre-leukemia establishment. To address its role for leukemic cell survival, we applied RNA interference to silence TEL/AML1 in leukemic cells. We designed and tested 11 different oligonucleotides targeting the TEL/AML1 fusion site. Using most efficient siRNAs, we achieved an average of 74-86% TEL/AML1 protein knockdown in REH and UOC-B6 leukemic cells, respectively. TEL/AML1 silencing neither decreased cell viability, nor induced apoptosis. On the contrary, it resulted in the modest but significant increase in the S phase fraction and in higher proliferation rate. Opposite effects on cell cycle distribution and proliferation were induced by AML1 silencing, thus, supporting our hypothesis that TEL/AML1 may block AML1-mediated promotion of G1/S progression through the cell cycle. In line with the lack of major effect on phenotype, we found no significant changes in clonogenic potential and global gene expression pattern upon TEL/AML1 depletion. Our data suggest that though TEL/AML1 is important for the (pre)leukemic clone development, it may be dispensable for leukemic cell survival and would not be a suitable target for gene-specific therapy. Leukemia (2011) 25, 313-320; doi:10.1038/leu.2010.277; published online 26 November 2010
- Translocation (12;21), the most frequent chromosomal aberration in childhood acute lymphoblastic leukemia, creates TEL/AML1 fusion gene. Resulting hybrid protein was shown to have a role in pre-leukemia establishment. To address its role for leukemic cell survival, we applied RNA interference to silence TEL/AML1 in leukemic cells. We designed and tested 11 different oligonucleotides targeting the TEL/AML1 fusion site. Using most efficient siRNAs, we achieved an average of 74-86% TEL/AML1 protein knockdown in REH and UOC-B6 leukemic cells, respectively. TEL/AML1 silencing neither decreased cell viability, nor induced apoptosis. On the contrary, it resulted in the modest but significant increase in the S phase fraction and in higher proliferation rate. Opposite effects on cell cycle distribution and proliferation were induced by AML1 silencing, thus, supporting our hypothesis that TEL/AML1 may block AML1-mediated promotion of G1/S progression through the cell cycle. In line with the lack of major effect on phenotype, we found no significant changes in clonogenic potential and global gene expression pattern upon TEL/AML1 depletion. Our data suggest that though TEL/AML1 is important for the (pre)leukemic clone development, it may be dispensable for leukemic cell survival and would not be a suitable target for gene-specific therapy. Leukemia (2011) 25, 313-320; doi:10.1038/leu.2010.277; published online 26 November 2010 (en)
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Title
| - Revealing the role of TEL/AML1 for leukemic cell survival by RNAi-mediated silencing
- Revealing the role of TEL/AML1 for leukemic cell survival by RNAi-mediated silencing (en)
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skos:prefLabel
| - Revealing the role of TEL/AML1 for leukemic cell survival by RNAi-mediated silencing
- Revealing the role of TEL/AML1 for leukemic cell survival by RNAi-mediated silencing (en)
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skos:notation
| - RIV/00064203:_____/11:6964!RIV12-MZ0-00064203
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http://linked.open...avai/riv/aktivita
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http://linked.open...avai/riv/aktivity
| - Z(MSM0021620813), Z(MZ0FNM2005)
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http://linked.open...iv/cisloPeriodika
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http://linked.open...vai/riv/dodaniDat
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http://linked.open...aciTvurceVysledku
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http://linked.open.../riv/druhVysledku
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http://linked.open...iv/duvernostUdaju
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http://linked.open...titaPredkladatele
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http://linked.open...dnocenehoVysledku
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http://linked.open...ai/riv/idVysledku
| - RIV/00064203:_____/11:6964
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http://linked.open...riv/jazykVysledku
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http://linked.open.../riv/klicovaSlova
| - acute lymphoblastic leukemia; TEL/AML1; fusion gene; RNAi; childhood leukemia; acute lymphoblastic-leukemia; polymerase-chain-reaction; fusion gene; preleukemic activity; tel-aml1; differentiation; promoter; t(12/21); protein; translocations (en)
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http://linked.open.../riv/klicoveSlovo
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http://linked.open...odStatuVydavatele
| - GB - Spojené království Velké Británie a Severního Irska
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http://linked.open...ontrolniKodProRIV
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http://linked.open...i/riv/nazevZdroje
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http://linked.open...in/vavai/riv/obor
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http://linked.open...ichTvurcuVysledku
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http://linked.open...cetTvurcuVysledku
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http://linked.open...UplatneniVysledku
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http://linked.open...v/svazekPeriodika
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http://linked.open...iv/tvurceVysledku
| - Trka, Jan
- Cario, G.
- Madžo, Jozef
- Žaliová, Markéta
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http://linked.open...ain/vavai/riv/wos
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http://linked.open...n/vavai/riv/zamer
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issn
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number of pages
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