Analysis of 5-Azacytidine Resistance Models Reveals a Set of Targetable Pathways
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00557510" target="_blank" >RIV/68378050:_____/22:00557510 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00216208:11110/22:10442470 RIV/00064165:_____/22:10442470
Výsledek na webu
<a href="https://www.mdpi.com/2073-4409/11/2/223" target="_blank" >https://www.mdpi.com/2073-4409/11/2/223</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/cells11020223" target="_blank" >10.3390/cells11020223</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Analysis of 5-Azacytidine Resistance Models Reveals a Set of Targetable Pathways
Popis výsledku v původním jazyce
The mechanisms by which myelodysplastic syndrome (MDS) cells resist the effects of hypomethylating agents (HMA) are currently the subject of intensive research. A better understanding of mechanisms by which the MDS cell becomes to tolerate HMA and progresses to acute myeloid leukemia (AML) requires the development of new cellular models. From MDS/AML cell lines we developed a model of 5-azacytidine (AZA) resistance whose stability was validated by a transplantation approach into immunocompromised mice. When investigating mRNA expression and DNA variants of the AZA resistant phenotype we observed deregulation of several cancer-related pathways including the phosphatidylinosito-3 kinase signaling. We have further shown that these pathways can be modulated by specific inhibitors that, while blocking the proliferation of AZA resistant cells, are unable to increase their sensitivity to AZA. Our data reveal a set of molecular mechanisms that can be targeted to expand therapeutic options during progression on AZA therapy.
Název v anglickém jazyce
Analysis of 5-Azacytidine Resistance Models Reveals a Set of Targetable Pathways
Popis výsledku anglicky
The mechanisms by which myelodysplastic syndrome (MDS) cells resist the effects of hypomethylating agents (HMA) are currently the subject of intensive research. A better understanding of mechanisms by which the MDS cell becomes to tolerate HMA and progresses to acute myeloid leukemia (AML) requires the development of new cellular models. From MDS/AML cell lines we developed a model of 5-azacytidine (AZA) resistance whose stability was validated by a transplantation approach into immunocompromised mice. When investigating mRNA expression and DNA variants of the AZA resistant phenotype we observed deregulation of several cancer-related pathways including the phosphatidylinosito-3 kinase signaling. We have further shown that these pathways can be modulated by specific inhibitors that, while blocking the proliferation of AZA resistant cells, are unable to increase their sensitivity to AZA. Our data reveal a set of molecular mechanisms that can be targeted to expand therapeutic options during progression on AZA therapy.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10601 - Cell biology
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2022
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Cells
ISSN
2073-4409
e-ISSN
2073-4409
Svazek periodika
11
Číslo periodika v rámci svazku
2
Stát vydavatele periodika
CH - Švýcarská konfederace
Počet stran výsledku
13
Strana od-do
223
Kód UT WoS článku
000757973600001
EID výsledku v databázi Scopus
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