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Statements

Subject Item
n2:RIV%2F00216224%3A14330%2F10%3A00044247%21RIV11-MSM-14330___
rdf:type
n7:Vysledek skos:Concept
dcterms:description
Chronic myeloid leukaemia (CML) is a clonal disorder of haematopoietic stem cells, characterized by the BCR-ABL oncogene. The BCR-ABL oncogene encodes constitutively active tyrosin kinase. It was previously shown, that transient inhibition of BCR-ABL by dasatinib is sufficient to commit CML cells to apoptosis (Shah 2008). Dasatinib mediated apoptosis in K562 cell line is accompanied by increasing expression level of proapoptotic protein BIM. Our results confirmed high mRNA levels of BIM in both transiently and continuously treated (100nM dasatinib) K562 cells compared to low dose continuous (1nM) dasatinib treatment. Intracellular level of BIM protein is regulated via phosphorylation by ERK protein kinase and subsequent degradation in the proteasome. In our research, we inhibited proteasome degradation by bortezomib. Combination of dasatinib and bortezomib led to rapid increase in BIM expression after 20 minutes. Chronic myeloid leukaemia (CML) is a clonal disorder of haematopoietic stem cells, characterized by the BCR-ABL oncogene. The BCR-ABL oncogene encodes constitutively active tyrosin kinase. It was previously shown, that transient inhibition of BCR-ABL by dasatinib is sufficient to commit CML cells to apoptosis (Shah 2008). Dasatinib mediated apoptosis in K562 cell line is accompanied by increasing expression level of proapoptotic protein BIM. Our results confirmed high mRNA levels of BIM in both transiently and continuously treated (100nM dasatinib) K562 cells compared to low dose continuous (1nM) dasatinib treatment. Intracellular level of BIM protein is regulated via phosphorylation by ERK protein kinase and subsequent degradation in the proteasome. In our research, we inhibited proteasome degradation by bortezomib. Combination of dasatinib and bortezomib led to rapid increase in BIM expression after 20 minutes.
dcterms:title
Dasatinib suppresses MEK/ERK pathway activity without sustained BCR-ABL inhibition and promotes BIM dependent apoptosis in chronic myeloid leukaemia cells. Dasatinib suppresses MEK/ERK pathway activity without sustained BCR-ABL inhibition and promotes BIM dependent apoptosis in chronic myeloid leukaemia cells.
skos:prefLabel
Dasatinib suppresses MEK/ERK pathway activity without sustained BCR-ABL inhibition and promotes BIM dependent apoptosis in chronic myeloid leukaemia cells. Dasatinib suppresses MEK/ERK pathway activity without sustained BCR-ABL inhibition and promotes BIM dependent apoptosis in chronic myeloid leukaemia cells.
skos:notation
RIV/00216224:14330/10:00044247!RIV11-MSM-14330___
n3:aktivita
n14:P
n3:aktivity
P(2B06052)
n3:dodaniDat
n9:2011
n3:domaciTvurceVysledku
n4:3715434 n4:4748891 n4:8054142 n4:3922014 n4:3021475 n4:4376285 n4:2346257
n3:druhVysledku
n15:O
n3:duvernostUdaju
n16:S
n3:entitaPredkladatele
n17:predkladatel
n3:idSjednocenehoVysledku
252923
n3:idVysledku
RIV/00216224:14330/10:00044247
n3:jazykVysledku
n11:eng
n3:klicovaSlova
dasatinib; CML
n3:klicoveSlovo
n8:dasatinib n8:CML
n3:kontrolniKodProRIV
[A0521E840F4F]
n3:obor
n12:FD
n3:pocetDomacichTvurcuVysledku
7
n3:pocetTvurcuVysledku
7
n3:projekt
n6:2B06052
n3:rokUplatneniVysledku
n9:2010
n3:tvurceVysledku
Kozubek, Michal Ráčil, Zdeněk Peterková, Martina Mayer, Jiří Šimara, Pavel Stejskal, Stanislav Krontorád Koutná, Irena
n13:organizacniJednotka
14330