About: The MEK inhibitor PD184352 enhances BMS-214662-induced apoptosis in CD34+ CML stem/progenitor cells

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About: The MEK inhibitor PD184352 enhances BMS-214662-induced apoptosis in CD34+ CML stem/progenitor cells Goto Sponge NotDistinct Permalink

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Attributes	Values
rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	The cytotoxic farnesyl transferase inhibitor BMS-214662 has been shown to potently induce mitochondrial apoptosis in primitive CD34+ chronic myeloid leukaemia (CML) stem/progenitor cells. Here, to enhance the BMS-214662 apoptotic effect, we further targeted the extracellular signal-regulated kinase (ERK) pathway, downstream of BCR–ABL, by treating CD34+ CML stem/progenitor cells with a highly selective adenosine triphosphate (ATP) non-competitive MEK inhibitor, PD184352. PD184352 increased the apoptotic effect of BMS-214662 in a CML blast crisis cell line, K562, and in primary chronic phase CD34+ CML cells. Compared with BMS-214662, after combination treatment we observed inhibition of ERK phosphorylation, increased Annexin-V levels, caspase-3, -8 and -9 activation and potentiated mitochondrial damage, associated with decreased levels of anti-apoptotic BCL-2 family protein MCL-1. The cytotoxic farnesyl transferase inhibitor BMS-214662 has been shown to potently induce mitochondrial apoptosis in primitive CD34+ chronic myeloid leukaemia (CML) stem/progenitor cells. Here, to enhance the BMS-214662 apoptotic effect, we further targeted the extracellular signal-regulated kinase (ERK) pathway, downstream of BCR–ABL, by treating CD34+ CML stem/progenitor cells with a highly selective adenosine triphosphate (ATP) non-competitive MEK inhibitor, PD184352. PD184352 increased the apoptotic effect of BMS-214662 in a CML blast crisis cell line, K562, and in primary chronic phase CD34+ CML cells. Compared with BMS-214662, after combination treatment we observed inhibition of ERK phosphorylation, increased Annexin-V levels, caspase-3, -8 and -9 activation and potentiated mitochondrial damage, associated with decreased levels of anti-apoptotic BCL-2 family protein MCL-1. (en)
Title	The MEK inhibitor PD184352 enhances BMS-214662-induced apoptosis in CD34+ CML stem/progenitor cells The MEK inhibitor PD184352 enhances BMS-214662-induced apoptosis in CD34+ CML stem/progenitor cells (en)
skos:prefLabel	The MEK inhibitor PD184352 enhances BMS-214662-induced apoptosis in CD34+ CML stem/progenitor cells The MEK inhibitor PD184352 enhances BMS-214662-induced apoptosis in CD34+ CML stem/progenitor cells (en)
skos:notation	RIV/00216224:14330/11:00067303!RIV14-MSM-14330___
http://linked.open...avai/riv/aktivita	P Z
http://linked.open...avai/riv/aktivity	P(2B06052), Z(MSM0021622430)
http://linked.open...iv/cisloPeriodika	7
http://linked.open...vai/riv/dodaniDat	2014
http://linked.open...aciTvurceVysledku	Šimara, Pavel
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Masarykova univerzita / Fakulta informatiky
http://linked.open...dnocenehoVysledku	211410
http://linked.open...ai/riv/idVysledku	RIV/00216224:14330/11:00067303
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	CML; BMS-214662; MEK inhibitor; PD184352; HSC; TKI (en)
http://linked.open.../riv/klicoveSlovo	CML HSC BMS-214662 MEK inhibitor PD184352 TKI
http://linked.open...odStatuVydavatele	GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV	[5F16768A07ED]
http://linked.open...i/riv/nazevZdroje	Leukemia
http://linked.open...in/vavai/riv/obor	FD
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	7 (xsd:int)
http://linked.open...vavai/riv/projekt	Determination of markers, screening and early diagnostics of cancer diseases using highly automated processing of multidimensional biomedical images
http://linked.open...UplatneniVysledku	2011
http://linked.open...v/svazekPeriodika	25
http://linked.open...iv/tvurceVysledku	Copland, Mhairi Grant, Steven Helgason, Gudmundur Vignir Holyoake, Tessa Pellicano, Francesca Sinclair, Amy Šimara, Pavel
http://linked.open...ain/vavai/riv/wos	000292682600012
http://linked.open...n/vavai/riv/zamer	Functional and molecular characteristics of cancer and normal stem cells - identification of targets for novel therapeutics and therapeutic strategies
issn	0887-6924
number of pages	9 (xsd:int)
http://bibframe.org/vocab/doi	10.1038/leu.2011.67
http://localhost/t...ganizacniJednotka	14330

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