Omacetaxine mepesuccinate prevents cytokine-dependent resistance to nilotinib in vitro: potential role of the common β-subunit c of cytokine receptors
Overcoming resistance against BCR-ABL-inhibitors in chronic myeloid leukemia (CML) is central to prevent progression to advanced phase disease. Kinase mutations of BCR-ABL and cytokine-mediated modulation of response to tyrosine kinase inhibitors (TKIs) are key mechanisms governing clinical response...
Gespeichert in:
| Hauptverfasser: | , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
13 January 2012
|
| In: |
Leukemia
Year: 2012, Jahrgang: 26, Heft: 6, Pages: 1321-1328 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/leu.2011.380 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1038/leu.2011.380 Verlag, Volltext: https://www.nature.com/articles/leu2011380 
|
| Verfasserangaben: | T. Klag, N. Härtel, P. Erben, J. Schwaab, U. Schnetzke, T. Schenk, A. Hochhaus, P. La Rosée |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1587207680 | ||
| 003 | DE-627 | ||
| 005 | 20230427034227.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 190204s2012 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/leu.2011.380 |2 doi | |
| 035 | |a (DE-627)1587207680 | ||
| 035 | |a (DE-576)517207680 | ||
| 035 | |a (DE-599)BSZ517207680 | ||
| 035 | |a (OCoLC)1341035120 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Klag, Thomas-Matthias |d 1981- |e VerfasserIn |0 (DE-588)14052942X |0 (DE-627)618918973 |0 (DE-576)31868098X |4 aut | |
| 245 | 1 | 0 | |a Omacetaxine mepesuccinate prevents cytokine-dependent resistance to nilotinib in vitro |b potential role of the common β-subunit c of cytokine receptors |c T. Klag, N. Härtel, P. Erben, J. Schwaab, U. Schnetzke, T. Schenk, A. Hochhaus, P. La Rosée |
| 264 | 1 | |c 13 January 2012 | |
| 300 | |a 8 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 04.02.2019 | ||
| 520 | |a Overcoming resistance against BCR-ABL-inhibitors in chronic myeloid leukemia (CML) is central to prevent progression to advanced phase disease. Kinase mutations of BCR-ABL and cytokine-mediated modulation of response to tyrosine kinase inhibitors (TKIs) are key mechanisms governing clinical response to imatinib and second generation TKIs. Omacetaxine mepesuccinate is effective in imatinib-resistant CML with reported stem cell activity. We specifically thought to explore omacetaxine in the context of the pan-resistant mutant T315I, and in its potential to modify cytokine-dependent resistance. Omacetaxine was investigated in cell lines and primary CD34+ enriched progenitor cells from patients with CML. Addition of cytokines, shown to revert the efficacy of TKIs in BCR-ABL-positive cells, does not affect omacetaxine mediated antiproliferative activity, neither in cell lines nor in primary CML CD34+ progenitor cells. Looking at potential mechanisms, we found marked downregulation of the common β-subunit c of the cytokine-receptors (cCRβc) for IL3, IL5 and GM-CSF by omacetaxine in cell lines and primary progenitor cultures. The observed cytokine-independent in-vitro cytotoxicity of omacetaxine may be explained by downregulation of cCRβc. Whether this can be used clinically as a means to optimize the stem cell activity of TKIs merits further evaluation. | ||
| 700 | 1 | |a Härtel, Nicolai |d 1977- |e VerfasserIn |0 (DE-588)129912913 |0 (DE-627)483650609 |0 (DE-576)297899821 |4 aut | |
| 700 | 1 | |a Erben, Philipp |d 1973- |e VerfasserIn |0 (DE-588)128501014 |0 (DE-627)373920997 |0 (DE-576)297181661 |4 aut | |
| 700 | 1 | |a Schwaab, Juliana |d 1982- |e VerfasserIn |0 (DE-588)1051912687 |0 (DE-627)787019399 |0 (DE-576)407558764 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Leukemia |d London : Springer Nature, 1997 |g 26(2012), 6, Seite 1321-1328 |h Online-Ressource |w (DE-627)32046699X |w (DE-600)2008023-2 |w (DE-576)094139733 |x 1476-5551 |7 nnas |a Omacetaxine mepesuccinate prevents cytokine-dependent resistance to nilotinib in vitro potential role of the common β-subunit c of cytokine receptors |
| 773 | 1 | 8 | |g volume:26 |g year:2012 |g number:6 |g pages:1321-1328 |g extent:8 |a Omacetaxine mepesuccinate prevents cytokine-dependent resistance to nilotinib in vitro potential role of the common β-subunit c of cytokine receptors |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/leu.2011.380 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u https://www.nature.com/articles/leu2011380 |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20190204 | ||
| 993 | |a Article | ||
| 994 | |a 2012 | ||
| 998 | |g 1051912687 |a Schwaab, Juliana |m 1051912687:Schwaab, Juliana |d 60000 |d 61200 |e 60000PS1051912687 |e 61200PS1051912687 |k 0/60000/ |k 1/60000/61200/ |p 4 | ||
| 998 | |g 128501014 |a Erben, Philipp |m 128501014:Erben, Philipp |d 60000 |d 61200 |e 60000PE128501014 |e 61200PE128501014 |k 0/60000/ |k 1/60000/61200/ |p 3 | ||
| 998 | |g 129912913 |a Härtel, Nicolai |m 129912913:Härtel, Nicolai |d 60000 |d 61200 |e 60000PH129912913 |e 61200PH129912913 |k 0/60000/ |k 1/60000/61200/ |p 2 | ||
| 999 | |a KXP-PPN1587207680 |e 3053757273 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"name":{"displayForm":["T. Klag, N. Härtel, P. Erben, J. Schwaab, U. Schnetzke, T. Schenk, A. Hochhaus, P. La Rosée"]},"note":["Gesehen am 04.02.2019"],"recId":"1587207680","physDesc":[{"extent":"8 S."}],"person":[{"role":"aut","display":"Klag, Thomas-Matthias","family":"Klag","given":"Thomas-Matthias"},{"given":"Nicolai","display":"Härtel, Nicolai","family":"Härtel","role":"aut"},{"role":"aut","given":"Philipp","family":"Erben","display":"Erben, Philipp"},{"role":"aut","display":"Schwaab, Juliana","family":"Schwaab","given":"Juliana"}],"title":[{"title_sort":"Omacetaxine mepesuccinate prevents cytokine-dependent resistance to nilotinib in vitro","title":"Omacetaxine mepesuccinate prevents cytokine-dependent resistance to nilotinib in vitro","subtitle":"potential role of the common β-subunit c of cytokine receptors"}],"relHost":[{"title":[{"subtitle":"normal and malignant hemopoiesis ; a peer-reviewed journal","title":"Leukemia","title_sort":"Leukemia"}],"physDesc":[{"extent":"Online-Ressource"}],"part":{"issue":"6","year":"2012","extent":"8","pages":"1321-1328","text":"26(2012), 6, Seite 1321-1328","volume":"26"},"origin":[{"publisherPlace":"London ; Basingstoke [u.a.] ; Basingstoke","dateIssuedDisp":"1997-","publisher":"Springer Nature ; Stockton Press ; Nature Publ. Group","dateIssuedKey":"1997"}],"id":{"eki":["32046699X"],"zdb":["2008023-2"],"issn":["1476-5551"]},"language":["eng"],"type":{"bibl":"periodical","media":"Online-Ressource"},"pubHistory":["Nachgewiesen 11.1997 -"],"note":["Gesehen am 15.03.04"],"recId":"32046699X","disp":"Omacetaxine mepesuccinate prevents cytokine-dependent resistance to nilotinib in vitro potential role of the common β-subunit c of cytokine receptorsLeukemia"}],"id":{"doi":["10.1038/leu.2011.380"],"eki":["1587207680"]},"language":["eng"],"type":{"bibl":"article-journal","media":"Online-Ressource"},"origin":[{"dateIssuedKey":"2012","dateIssuedDisp":"13 January 2012"}]} | ||
| SRT | |a KLAGTHOMASOMACETAXIN1320 | ||