EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells.
Overexpression of ecotropic viral integration site 1 (EVI1) is associated with aggressive disease in acute myeloid leukemia (AML). Despite of its clinical importance, little is known about the mechanism through which EVI1 confers resistance to antileukemic drugs. Here, we show that a human myeloid c...
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2013
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oai:doaj.org-article:585c0852f1d94e859d4e2ecfd8b609762021-11-18T07:57:27ZEVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells.1932-620310.1371/journal.pone.0056308https://doaj.org/article/585c0852f1d94e859d4e2ecfd8b609762013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23457546/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Overexpression of ecotropic viral integration site 1 (EVI1) is associated with aggressive disease in acute myeloid leukemia (AML). Despite of its clinical importance, little is known about the mechanism through which EVI1 confers resistance to antileukemic drugs. Here, we show that a human myeloid cell line constitutively overexpressing EVI1 after infection with a retroviral vector (U937_EVI1) was partially resistant to etoposide and daunorubicin as compared to empty vector infected control cells (U937_vec). Similarly, inducible expression of EVI1 in HL-60 cells decreased their sensitivity to daunorubicin. Gene expression microarray analyses of U937_EVI1 and U937_vec cells cultured in the absence or presence of etoposide showed that 77 and 419 genes were regulated by EVI1 and etoposide, respectively. Notably, mRNA levels of 26 of these genes were altered by both stimuli, indicating that EVI1 regulated genes were strongly enriched among etoposide regulated genes and vice versa. One of the genes that were induced by both EVI1 and etoposide was CDKN1A/p21/WAF, which in addition to its function as a cell cycle regulator plays an important role in conferring chemotherapy resistance in various tumor types. Indeed, overexpression of CDKN1A in U937 cells mimicked the phenotype of EVI1 overexpression, similarly conferring partial resistance to antileukemic drugs.Anna RommerBirgit SteinmetzFriederike HerbstHubert HacklPetra HeffeterDaniela HeilosMartin FilipitsKatarina SteinleitnerShayda HemmatiIrene HerbacekIlse SchwarzingerKatharina HartlPieter RondouHanno GlimmKadin KarakayaAlwin KrämerWalter BergerRotraud WieserPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56308 (2013) |
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DOAJ |
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Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Anna Rommer Birgit Steinmetz Friederike Herbst Hubert Hackl Petra Heffeter Daniela Heilos Martin Filipits Katarina Steinleitner Shayda Hemmati Irene Herbacek Ilse Schwarzinger Katharina Hartl Pieter Rondou Hanno Glimm Kadin Karakaya Alwin Krämer Walter Berger Rotraud Wieser EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells. |
| description |
Overexpression of ecotropic viral integration site 1 (EVI1) is associated with aggressive disease in acute myeloid leukemia (AML). Despite of its clinical importance, little is known about the mechanism through which EVI1 confers resistance to antileukemic drugs. Here, we show that a human myeloid cell line constitutively overexpressing EVI1 after infection with a retroviral vector (U937_EVI1) was partially resistant to etoposide and daunorubicin as compared to empty vector infected control cells (U937_vec). Similarly, inducible expression of EVI1 in HL-60 cells decreased their sensitivity to daunorubicin. Gene expression microarray analyses of U937_EVI1 and U937_vec cells cultured in the absence or presence of etoposide showed that 77 and 419 genes were regulated by EVI1 and etoposide, respectively. Notably, mRNA levels of 26 of these genes were altered by both stimuli, indicating that EVI1 regulated genes were strongly enriched among etoposide regulated genes and vice versa. One of the genes that were induced by both EVI1 and etoposide was CDKN1A/p21/WAF, which in addition to its function as a cell cycle regulator plays an important role in conferring chemotherapy resistance in various tumor types. Indeed, overexpression of CDKN1A in U937 cells mimicked the phenotype of EVI1 overexpression, similarly conferring partial resistance to antileukemic drugs. |
| format |
article |
| author |
Anna Rommer Birgit Steinmetz Friederike Herbst Hubert Hackl Petra Heffeter Daniela Heilos Martin Filipits Katarina Steinleitner Shayda Hemmati Irene Herbacek Ilse Schwarzinger Katharina Hartl Pieter Rondou Hanno Glimm Kadin Karakaya Alwin Krämer Walter Berger Rotraud Wieser |
| author_facet |
Anna Rommer Birgit Steinmetz Friederike Herbst Hubert Hackl Petra Heffeter Daniela Heilos Martin Filipits Katarina Steinleitner Shayda Hemmati Irene Herbacek Ilse Schwarzinger Katharina Hartl Pieter Rondou Hanno Glimm Kadin Karakaya Alwin Krämer Walter Berger Rotraud Wieser |
| author_sort |
Anna Rommer |
| title |
EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells. |
| title_short |
EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells. |
| title_full |
EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells. |
| title_fullStr |
EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells. |
| title_full_unstemmed |
EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells. |
| title_sort |
evi1 inhibits apoptosis induced by antileukemic drugs via upregulation of cdkn1a/p21/waf in human myeloid cells. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/585c0852f1d94e859d4e2ecfd8b60976 |
| work_keys_str_mv |
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