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GATA2 regulates the erythropoietin receptor in t(12;21) ALL
The t(12;21) (p13;q22) chromosomal translocation resulting in the fusion gene is the most frequent structural cytogenetic abnormality in children with acute lymphoblastic leukemia (ALL). The erythropoietin receptor (EPOR), usually associated with erythroid progenitor cells, is highly expressed in po...
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| Published in: | Oncotarget 2017-09, Vol.8 (39), p.66061-66074 |
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| creator | Gaine, Marie E Sharpe, Daniel J Smith, James S Colyer, Hilary A A Hodges, Vivien M Lappin, Terry R Mills, Ken I |
| description | The t(12;21) (p13;q22) chromosomal translocation resulting in the
fusion gene is the most frequent structural cytogenetic abnormality in children with acute lymphoblastic leukemia (ALL). The erythropoietin receptor (EPOR), usually associated with erythroid progenitor cells, is highly expressed in
positive cases compared to other B-lineage ALL subtypes. Gene expression analysis of a microarray database and direct quantitative analysis of patient samples revealed strong correlation between
and
expression in ALL, and higher expression of
in t(12;21) patients. The mechanism of EPOR regulation was mainly investigated using two B-ALL cell lines: REH, which harbor and express the
fusion gene; and NALM-6, which do not. Expression of EPOR was increased in REH cells compared to NALM-6 cells. Moreover, of the six GATA family members only
was differentially expressed with substantially higher levels present in REH cells.
was shown to bind to the EPOR 5'-UTR in REH, but did not bind in NALM-6 cells. Overexpression of
led to an increase in EPOR expression in REH cells only, indicating that GATA2 regulates EPOR but is dependent on the cellular context. Both
and
are hypomethylated and associated with increased mRNA expression in REH compared to NALM-6 cells. Decitabine treatment effectively reduced methylation of CpG sites in the
promoter leading to increased
expression in both cell lines. Although Decitabine also reduced an already low level of methylation of the EPOR in NALM-6 cells there was no increase in EPOR expression. Furthermore,
and
are regulated post-transcriptionally by miR-362 and miR-650, respectively. Overall our data show that EPOR expression in t(12;21) B-ALL cells, is regulated by GATA2 and is mediated through epigenetic, transcriptional and post-transcriptional mechanisms, contingent upon the genetic subtype of the disease. |
| doi_str_mv | 10.18632/oncotarget.19792 |
| format | article |
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fusion gene is the most frequent structural cytogenetic abnormality in children with acute lymphoblastic leukemia (ALL). The erythropoietin receptor (EPOR), usually associated with erythroid progenitor cells, is highly expressed in
positive cases compared to other B-lineage ALL subtypes. Gene expression analysis of a microarray database and direct quantitative analysis of patient samples revealed strong correlation between
and
expression in ALL, and higher expression of
in t(12;21) patients. The mechanism of EPOR regulation was mainly investigated using two B-ALL cell lines: REH, which harbor and express the
fusion gene; and NALM-6, which do not. Expression of EPOR was increased in REH cells compared to NALM-6 cells. Moreover, of the six GATA family members only
was differentially expressed with substantially higher levels present in REH cells.
was shown to bind to the EPOR 5'-UTR in REH, but did not bind in NALM-6 cells. Overexpression of
led to an increase in EPOR expression in REH cells only, indicating that GATA2 regulates EPOR but is dependent on the cellular context. Both
and
are hypomethylated and associated with increased mRNA expression in REH compared to NALM-6 cells. Decitabine treatment effectively reduced methylation of CpG sites in the
promoter leading to increased
expression in both cell lines. Although Decitabine also reduced an already low level of methylation of the EPOR in NALM-6 cells there was no increase in EPOR expression. Furthermore,
and
are regulated post-transcriptionally by miR-362 and miR-650, respectively. Overall our data show that EPOR expression in t(12;21) B-ALL cells, is regulated by GATA2 and is mediated through epigenetic, transcriptional and post-transcriptional mechanisms, contingent upon the genetic subtype of the disease.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.19792</identifier><identifier>PMID: 29029492</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Research Paper</subject><ispartof>Oncotarget, 2017-09, Vol.8 (39), p.66061-66074</ispartof><rights>Copyright: © 2017 Gaine et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-8da798d486a598442afcaec71989743b642f2b584e91e6945fa4a445321c6ac73</citedby><cites>FETCH-LOGICAL-c356t-8da798d486a598442afcaec71989743b642f2b584e91e6945fa4a445321c6ac73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630392/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630392/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29029492$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gaine, Marie E</creatorcontrib><creatorcontrib>Sharpe, Daniel J</creatorcontrib><creatorcontrib>Smith, James S</creatorcontrib><creatorcontrib>Colyer, Hilary A A</creatorcontrib><creatorcontrib>Hodges, Vivien M</creatorcontrib><creatorcontrib>Lappin, Terry R</creatorcontrib><creatorcontrib>Mills, Ken I</creatorcontrib><title>GATA2 regulates the erythropoietin receptor in t(12;21) ALL</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>The t(12;21) (p13;q22) chromosomal translocation resulting in the
fusion gene is the most frequent structural cytogenetic abnormality in children with acute lymphoblastic leukemia (ALL). The erythropoietin receptor (EPOR), usually associated with erythroid progenitor cells, is highly expressed in
positive cases compared to other B-lineage ALL subtypes. Gene expression analysis of a microarray database and direct quantitative analysis of patient samples revealed strong correlation between
and
expression in ALL, and higher expression of
in t(12;21) patients. The mechanism of EPOR regulation was mainly investigated using two B-ALL cell lines: REH, which harbor and express the
fusion gene; and NALM-6, which do not. Expression of EPOR was increased in REH cells compared to NALM-6 cells. Moreover, of the six GATA family members only
was differentially expressed with substantially higher levels present in REH cells.
was shown to bind to the EPOR 5'-UTR in REH, but did not bind in NALM-6 cells. Overexpression of
led to an increase in EPOR expression in REH cells only, indicating that GATA2 regulates EPOR but is dependent on the cellular context. Both
and
are hypomethylated and associated with increased mRNA expression in REH compared to NALM-6 cells. Decitabine treatment effectively reduced methylation of CpG sites in the
promoter leading to increased
expression in both cell lines. Although Decitabine also reduced an already low level of methylation of the EPOR in NALM-6 cells there was no increase in EPOR expression. Furthermore,
and
are regulated post-transcriptionally by miR-362 and miR-650, respectively. Overall our data show that EPOR expression in t(12;21) B-ALL cells, is regulated by GATA2 and is mediated through epigenetic, transcriptional and post-transcriptional mechanisms, contingent upon the genetic subtype of the disease.</description><subject>Research Paper</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNpVUE1Lw0AQXUSxUvsDvEiO9ZCa_UyWghCKViHgpZ6X7XbSRtJs3N0I_feGttY6l3nwPmZ4CN3hZIIzQcmjbYwN2q0hTLBMJblAN1gyGRPO6eUZHqCR959JP5ylGZHXaEBkQnqa3KDpPF_kJHKw7modwEdhAxG4Xdg429oKQtX0pIE2WBf1OIwxmRL8EOVFcYuuSl17GB33EH28PC9mr3HxPn-b5UVsKBchzlY6ldmKZUJzmTFGdGk0mBTLTKaMLgUjJVnyjIHEICTjpWaaMU4JNkKblA7R0yG37ZZbWBlogtO1al211W6nrK7Uf6apNmptvxUXNKGS9AHjY4CzXx34oLaVN1DXugHbeYUlxwwLnNBeig9S46z3DsrTGZyofe_qr3e177333J__d3L8tkx_AIZdf5E</recordid><startdate>20170912</startdate><enddate>20170912</enddate><creator>Gaine, Marie E</creator><creator>Sharpe, Daniel J</creator><creator>Smith, James S</creator><creator>Colyer, Hilary A A</creator><creator>Hodges, Vivien M</creator><creator>Lappin, Terry R</creator><creator>Mills, Ken I</creator><general>Impact Journals LLC</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170912</creationdate><title>GATA2 regulates the erythropoietin receptor in t(12;21) ALL</title><author>Gaine, Marie E ; Sharpe, Daniel J ; Smith, James S ; Colyer, Hilary A A ; Hodges, Vivien M ; Lappin, Terry R ; Mills, Ken I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-8da798d486a598442afcaec71989743b642f2b584e91e6945fa4a445321c6ac73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Research Paper</topic><toplevel>online_resources</toplevel><creatorcontrib>Gaine, Marie E</creatorcontrib><creatorcontrib>Sharpe, Daniel J</creatorcontrib><creatorcontrib>Smith, James S</creatorcontrib><creatorcontrib>Colyer, Hilary A A</creatorcontrib><creatorcontrib>Hodges, Vivien M</creatorcontrib><creatorcontrib>Lappin, Terry R</creatorcontrib><creatorcontrib>Mills, Ken I</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gaine, Marie E</au><au>Sharpe, Daniel J</au><au>Smith, James S</au><au>Colyer, Hilary A A</au><au>Hodges, Vivien M</au><au>Lappin, Terry R</au><au>Mills, Ken I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GATA2 regulates the erythropoietin receptor in t(12;21) ALL</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-09-12</date><risdate>2017</risdate><volume>8</volume><issue>39</issue><spage>66061</spage><epage>66074</epage><pages>66061-66074</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>These two authors have contributed equally to the manuscript</notes><abstract>The t(12;21) (p13;q22) chromosomal translocation resulting in the
fusion gene is the most frequent structural cytogenetic abnormality in children with acute lymphoblastic leukemia (ALL). The erythropoietin receptor (EPOR), usually associated with erythroid progenitor cells, is highly expressed in
positive cases compared to other B-lineage ALL subtypes. Gene expression analysis of a microarray database and direct quantitative analysis of patient samples revealed strong correlation between
and
expression in ALL, and higher expression of
in t(12;21) patients. The mechanism of EPOR regulation was mainly investigated using two B-ALL cell lines: REH, which harbor and express the
fusion gene; and NALM-6, which do not. Expression of EPOR was increased in REH cells compared to NALM-6 cells. Moreover, of the six GATA family members only
was differentially expressed with substantially higher levels present in REH cells.
was shown to bind to the EPOR 5'-UTR in REH, but did not bind in NALM-6 cells. Overexpression of
led to an increase in EPOR expression in REH cells only, indicating that GATA2 regulates EPOR but is dependent on the cellular context. Both
and
are hypomethylated and associated with increased mRNA expression in REH compared to NALM-6 cells. Decitabine treatment effectively reduced methylation of CpG sites in the
promoter leading to increased
expression in both cell lines. Although Decitabine also reduced an already low level of methylation of the EPOR in NALM-6 cells there was no increase in EPOR expression. Furthermore,
and
are regulated post-transcriptionally by miR-362 and miR-650, respectively. Overall our data show that EPOR expression in t(12;21) B-ALL cells, is regulated by GATA2 and is mediated through epigenetic, transcriptional and post-transcriptional mechanisms, contingent upon the genetic subtype of the disease.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>29029492</pmid><doi>10.18632/oncotarget.19792</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| title | GATA2 regulates the erythropoietin receptor in t(12;21) ALL |
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