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Statements

Subject Item
n2:RIV%2F00064203%3A_____%2F12%3A8239%21RIV13-MZ0-00064203
rdf:type
skos:Concept n13:Vysledek
rdfs:seeAlso
http://dx.doi.org/10.1016/j.exphem.2012.04.005
dcterms:description
Childhood acute lymphoblastic leukemia (ALL) is treated with combined chemotherapy, including L-asparaginase (L-asp). Recent studies question the traditional view that the level of asparagine synthetase (ASNS), an enzyme producing the intracellular asparagine, correlates with the response to L-asp treatment. However, the importance of ASNS in response to L-asp has neither been confirmed nor refuted so far. In this study, we wanted to elucidate the effect of ASNS expression level on the sensitivity of ALL cells to L-asp treatment. We used four ALL cell lines (NALM-6, RS4;11, REH, and UOCB6) and 30 diagnostic bone marrow samples of ALL patients to study the relationship between ASNS expression and sensitivity to L-asp using MTS proliferation assay. RNA interference was used to study the effect of a range of ASNS levels on the response to L-asp treatment. Using a cell line model with a gradually knocked-down ASNS gene, we defined a cutoff level below which ASNS gene expression does not correlate with sensitivity to L-asp. Importantly, ASNS gene expression in patients' ALL blasts is below this level. We confirmed that there was no correlation between ASNS gene expression and sensitivity to L-asp in ALL blasts. In addition, we show that cells with low ASNS expression level do not respond to asparagine deprivation by upregulation of ASNS gene expression. In conclusion, the ASNS expression level does not predict sensitivity to L-asp in leukemic blasts. Moreover, cell lines with high basal expression of ASNS cannot serve as a valid model for studies on the relationship between the ASNS and L-asp cytotoxic effect. Childhood acute lymphoblastic leukemia (ALL) is treated with combined chemotherapy, including L-asparaginase (L-asp). Recent studies question the traditional view that the level of asparagine synthetase (ASNS), an enzyme producing the intracellular asparagine, correlates with the response to L-asp treatment. However, the importance of ASNS in response to L-asp has neither been confirmed nor refuted so far. In this study, we wanted to elucidate the effect of ASNS expression level on the sensitivity of ALL cells to L-asp treatment. We used four ALL cell lines (NALM-6, RS4;11, REH, and UOCB6) and 30 diagnostic bone marrow samples of ALL patients to study the relationship between ASNS expression and sensitivity to L-asp using MTS proliferation assay. RNA interference was used to study the effect of a range of ASNS levels on the response to L-asp treatment. Using a cell line model with a gradually knocked-down ASNS gene, we defined a cutoff level below which ASNS gene expression does not correlate with sensitivity to L-asp. Importantly, ASNS gene expression in patients' ALL blasts is below this level. We confirmed that there was no correlation between ASNS gene expression and sensitivity to L-asp in ALL blasts. In addition, we show that cells with low ASNS expression level do not respond to asparagine deprivation by upregulation of ASNS gene expression. In conclusion, the ASNS expression level does not predict sensitivity to L-asp in leukemic blasts. Moreover, cell lines with high basal expression of ASNS cannot serve as a valid model for studies on the relationship between the ASNS and L-asp cytotoxic effect.
dcterms:title
Low expression of asparagine synthetase in lymphoid blasts precludes its role in sensitivity to L-asparaginase Low expression of asparagine synthetase in lymphoid blasts precludes its role in sensitivity to L-asparaginase
skos:prefLabel
Low expression of asparagine synthetase in lymphoid blasts precludes its role in sensitivity to L-asparaginase Low expression of asparagine synthetase in lymphoid blasts precludes its role in sensitivity to L-asparaginase
skos:notation
RIV/00064203:_____/12:8239!RIV13-MZ0-00064203
n13:predkladatel
n14:ico%3A00064203
n3:aktivita
n6:Z n6:P
n3:aktivity
P(NT12429), Z(MSM0021620813)
n3:cisloPeriodika
8
n3:dodaniDat
n18:2013
n3:domaciTvurceVysledku
n4:5405769 n4:1071718
n3:druhVysledku
n11:J
n3:duvernostUdaju
n8:S
n3:entitaPredkladatele
n19:predkladatel
n3:idSjednocenehoVysledku
147489
n3:idVysledku
RIV/00064203:_____/12:8239
n3:jazykVysledku
n17:eng
n3:klicovaSlova
acute lymphoblastic-leukemia; cell-lines; in-vitro; drug-sensitivity; up-regulation; mtt-assay; resistance; children; gene; chemosensitivity
n3:klicoveSlovo
n5:children n5:gene n5:cell-lines n5:acute%20lymphoblastic-leukemia n5:up-regulation n5:resistance n5:mtt-assay n5:drug-sensitivity n5:chemosensitivity n5:in-vitro
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[90D335E666DE]
n3:nazevZdroje
Experimental Hematology
n3:obor
n20:FD
n3:pocetDomacichTvurcuVysledku
2
n3:pocetTvurcuVysledku
4
n3:projekt
n16:NT12429
n3:rokUplatneniVysledku
n18:2012
n3:svazekPeriodika
40
n3:tvurceVysledku
Starková, Júlia Žaliová, Markéta Heřmanová, Ivana Trka, Jan
n3:wos
000307319500006
n3:zamer
n12:MSM0021620813
s:issn
0301-472X
s:numberOfPages
9