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Statements

Subject Item
n2:RIV%2F61989592%3A15110%2F08%3A00007430%21RIV09-MSM-15110___
rdf:type
n12:Vysledek skos:Concept
dcterms:description
Activation of Src family of kinases (SFK) is associated with chronic myeloid leukemia (CML) disease progression and resistance to imatinib (IM) therapy. Activation of SFK can be either Bcr-Abl-dependent or Bcr-Abl-independent in IM-resistant CML patients and clinical importance of this phenomenon is not completely understood. Second generation of tyrosine kinase inhibitors (TKIs) such as dasatinib, targeting both Bcr-Abl kinase as well as SFK, could represent a logical alternative for treatment of patients with acquired IM resistance due to SFK activation. Recent studies raised question whether overexpression of SFK could lead to an acquired resistance to dasatinib. Sensitivity of individual patients? leukemia cells to TKIs can be carried out by assessment of inhibition of phosphorylation of Crkl and SFK after incubation of patient?s leukocytes with the drug in vitro. We used 10 ?M IM or 250 nM dasatinib in vitro and detection with western blot analysis with anti-Crkl 32H4 monoclonal antibody (Cell Activation of Src family of kinases (SFK) is associated with chronic myeloid leukemia (CML) disease progression and resistance to imatinib (IM) therapy. Activation of SFK can be either Bcr-Abl-dependent or Bcr-Abl-independent in IM-resistant CML patients and clinical importance of this phenomenon is not completely understood. Second generation of tyrosine kinase inhibitors (TKIs) such as dasatinib, targeting both Bcr-Abl kinase as well as SFK, could represent a logical alternative for treatment of patients with acquired IM resistance due to SFK activation. Recent studies raised question whether overexpression of SFK could lead to an acquired resistance to dasatinib. Sensitivity of individual patients? leukemia cells to TKIs can be carried out by assessment of inhibition of phosphorylation of Crkl and SFK after incubation of patient?s leukocytes with the drug in vitro. We used 10 ?M IM or 250 nM dasatinib in vitro and detection with western blot analysis with anti-Crkl 32H4 monoclonal antibody (Cell Aktivace Src kináz (SFK) je úzce spjata s progresí nemoci chronická myeloidní leukémie (CML) a její rezistence na léčbu imatinibem (IM). Bylo prokázáno, že aktivace SFK může být u CML pacientů rezistentních na léčbu IM buď závislá nebo nezávislá na Bcr-Abl, tento fenomén však nebyl zatím blíže vysvětlen. Léčba inhibitory tyrozinkinázových kináz (TKI) druhé generace jako je dasatinib, které cíleně inhibují jak Bcr-Abl kinázu tak i SFK, pak může reprezentovat vhodnou alternativu k léčbě pacientů rezistentních na léčbu IM, u kterých byla zjištěna aktivace SFK. Poslední studie se tak zabývají otázkou, zda může zvýšené exprese SFK vést rovněž k získání rezistence na dasatinib.
dcterms:title
Bcr-Abl-independent activation of Src kinases associated with development of dasatinib resistance in a CML patient Bcr-Abl-independent activation of Src kinases associated with development of dasatinib resistance in a CML patient Rezistence na dasatinib u CML pacientů spojená s aktivací Src kináz nezávisle na Bcr-Abl
skos:prefLabel
Bcr-Abl-independent activation of Src kinases associated with development of dasatinib resistance in a CML patient Bcr-Abl-independent activation of Src kinases associated with development of dasatinib resistance in a CML patient Rezistence na dasatinib u CML pacientů spojená s aktivací Src kináz nezávisle na Bcr-Abl
skos:notation
RIV/61989592:15110/08:00007430!RIV09-MSM-15110___
n5:aktivita
n10:Z
n5:aktivity
Z(MSM6198959205)
n5:cisloPeriodika
11
n5:dodaniDat
n8:2009
n5:domaciTvurceVysledku
n6:2328356 n6:3461904 n6:9160329 n6:8141975 n6:2556049 n6:8478325 n6:5538912 n6:8539855 n6:7101813
n5:druhVysledku
n13:J
n5:duvernostUdaju
n11:S
n5:entitaPredkladatele
n15:predkladatel
n5:idSjednocenehoVysledku
357701
n5:idVysledku
RIV/61989592:15110/08:00007430
n5:jazykVysledku
n18:eng
n5:klicovaSlova
Bcr-Abl; Src kinase; dasatinib resistance; chronic myeloid leukemia
n5:klicoveSlovo
n7:Bcr-Abl n7:chronic%20myeloid%20leukemia n7:Src%20kinase n7:dasatinib%20resistance
n5:kodStatuVydavatele
US - Spojené státy americké
n5:kontrolniKodProRIV
[C80E8131ED33]
n5:nazevZdroje
Blood
n5:obor
n16:FD
n5:pocetDomacichTvurcuVysledku
9
n5:pocetTvurcuVysledku
9
n5:rokUplatneniVysledku
n8:2008
n5:svazekPeriodika
112
n5:tvurceVysledku
Veselovská, Jitka Jarošová, Marie Indrák, Karel Balcárková, Jana Urbánková, Helena Faber, Edgar Mojzíková, Renáta Holzerová, Milena Divoký, Vladimír
n5:zamer
n14:MSM6198959205
s:issn
0006-4971
s:numberOfPages
1
n17:organizacniJednotka
15110