Dasatinib Promotes BIM Dependent Apoptosis Via MEK/ERK without Need for Permanent BCR-ABL Inhibition

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14330%2F10%3A00046220" target="_blank" >RIV/00216224:14330/10:00046220 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Dasatinib Promotes BIM Dependent Apoptosis Via MEK/ERK without Need for Permanent BCR-ABL Inhibition

Popis výsledku v původním jazyce

Chronic myeloid leukaemia (CML) is a clonal disorder of haematopoietic stem cells, characterized by constitutively active BCR-ABL kinase. It was previously shown, that transient inhibition of BCR-ABL by tyrosin kinase inhibitor (TKI) dasatinib induces apoptosis in CML cells (Shah 2008). Dasatinib mediated apoptosis is accompanied by increasing expression level of proapoptotic protein BIM and inhibition of its degradation in proteasome. Our aim is to find alterations in BCR-ABL downstream pathways and changes in BIM expression after pulse (wash-out after 20min) or continuous treatment with TKI dasatinib alone or in combination with proteasome inhibitor bortezomib in K562 cells. Higher mRNA levels of BIM were confirmed in both transiently and continuously treated (100nM dasatinib) K562 cells compared to low dose continuous (1nM dasatinib) treatment.

Název v anglickém jazyce

Dasatinib Promotes BIM Dependent Apoptosis Via MEK/ERK without Need for Permanent BCR-ABL Inhibition

Popis výsledku anglicky

Chronic myeloid leukaemia (CML) is a clonal disorder of haematopoietic stem cells, characterized by constitutively active BCR-ABL kinase. It was previously shown, that transient inhibition of BCR-ABL by tyrosin kinase inhibitor (TKI) dasatinib induces apoptosis in CML cells (Shah 2008). Dasatinib mediated apoptosis is accompanied by increasing expression level of proapoptotic protein BIM and inhibition of its degradation in proteasome. Our aim is to find alterations in BCR-ABL downstream pathways and changes in BIM expression after pulse (wash-out after 20min) or continuous treatment with TKI dasatinib alone or in combination with proteasome inhibitor bortezomib in K562 cells. Higher mRNA levels of BIM were confirmed in both transiently and continuously treated (100nM dasatinib) K562 cells compared to low dose continuous (1nM dasatinib) treatment.

Druh

O - Ostatní výsledky

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

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Projekt

<a href="/cs/project/2B06052" target="_blank" >2B06052: Vytipování markerů, screening a časná diagnostika nádorových onemocnění pomocí vysoce automatizovaného zpracování multidimenzionálních biomedicínských obrazů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2010

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů