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  • Abnormality dvou genů, p53 nebo ATM, dvou kooperujících tumor-supresorových genů, prokazatleně zhoršují možnosti léčby u pacientů s chronickou lymfocytární leukémiíí (CLL). Ačkoli se tyto aberace zdají být u CLL navzájem se vylučujícící, inaktivace výše zmíněných genů vedek horší prognóze. Testovali jsme in vitro senzitivitu CLL vzorků s heterozygotní delecí ATM k fludarabinu a combinaci fludarabinu a rituximabu; odezvy byly srovnávány s bunňkami s abnormalitami v genu TP53 a S wild-type (wt) buňkam, abychom vymezili relativní význam delece ATM. Metody: Provedli jsme analýzu na 59 charakterizovaných CLL vzorcích pomocí WST-1 assay. Pro monitoring aktivace ATM/p53 dráhy byla použita metoda western-blottingu a kvantitativni real-time PCR. Výsledky a závěr: Vzorky a abnormalitami v TP53 genu při použití klinicky relevantní koncentrace fludarabinu vykazovaly výrazně vyšší rezistenci než ostatní CLL vzorky (p = 0,012); skupina vzorků s delecí ATM nebyla rezistentnější než wt vzorky. (cs)
  • Abnormalities of the TP53 or ATM, cooperating tumor-suppressor genes, significantly worsen the treatment options for chronic lymphocytic leukemia (CLL) patients. Although the aberrations seem to be mutually exclusive in this leukemia, inactivation of the former gene leads to worse prognosis. We tested the in vitro sensitivity of the CLL samples with heterozygous ATM deletion to fludarabine and combination of fludarabine and rituximab; the responses were compared with the TP53-abnormal and wild-type (wt) cells to delimitate relative significance of ATM deletion. METHODS: In vitro analysis was performed on fifty-nine characterized CLL samples using viability assay WST-1. Western blot and real-time RT-PCR were used to monitor the activation of the ATM/p53 pathway.
  • Abnormalities of the TP53 or ATM, cooperating tumor-suppressor genes, significantly worsen the treatment options for chronic lymphocytic leukemia (CLL) patients. Although the aberrations seem to be mutually exclusive in this leukemia, inactivation of the former gene leads to worse prognosis. We tested the in vitro sensitivity of the CLL samples with heterozygous ATM deletion to fludarabine and combination of fludarabine and rituximab; the responses were compared with the TP53-abnormal and wild-type (wt) cells to delimitate relative significance of ATM deletion. METHODS: In vitro analysis was performed on fifty-nine characterized CLL samples using viability assay WST-1. Western blot and real-time RT-PCR were used to monitor the activation of the ATM/p53 pathway. (en)
Title
  • Presence of heterozygous ATM deletion may not be critical in the primary response of chronic lymphocytic leukemia cells to
  • Přítomnost heterozygotní delece ATM nemusí být rozhodující v prvotní odpovědi buněk chronické lymfocytární leukémie na fludarabin (cs)
  • Presence of heterozygous ATM deletion may not be critical in the primary response of chronic lymphocytic leukemia cells to (en)
skos:prefLabel
  • Presence of heterozygous ATM deletion may not be critical in the primary response of chronic lymphocytic leukemia cells to
  • Přítomnost heterozygotní delece ATM nemusí být rozhodující v prvotní odpovědi buněk chronické lymfocytární leukémie na fludarabin (cs)
  • Presence of heterozygous ATM deletion may not be critical in the primary response of chronic lymphocytic leukemia cells to (en)
skos:notation
  • RIV/65269705:_____/09:#0000279!RIV09-MZ0-65269705
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(NR8445)
http://linked.open...iv/cisloPeriodika
  • 2
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 335768
http://linked.open...ai/riv/idVysledku
  • RIV/65269705:_____/09:#0000279
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • lymphocytic leukemia (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV
  • [E8218F9A0D82]
http://linked.open...i/riv/nazevZdroje
  • European Journal of Haematology
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 82
http://linked.open...iv/tvurceVysledku
  • Brychtová, Yvona
  • Doubek, Michael
  • Mayer, Jiří
  • Pospíšilová, Šárka
  • Trbušek, Martin
  • Šmardová, Jana
  • Klabusay, Martin
  • Borský, M.
  • Čejková, Soňa
http://linked.open...ain/vavai/riv/wos
  • 000262347300007
issn
  • 0902-4441
number of pages
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