| pubmed-article:15536149 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15536149 | lifeskim:mentions | umls-concept:C0023467 | lld:lifeskim |
| pubmed-article:15536149 | lifeskim:mentions | umls-concept:C0007589 | lld:lifeskim |
| pubmed-article:15536149 | lifeskim:mentions | umls-concept:C1510411 | lld:lifeskim |
| pubmed-article:15536149 | lifeskim:mentions | umls-concept:C0542341 | lld:lifeskim |
| pubmed-article:15536149 | lifeskim:mentions | umls-concept:C1335616 | lld:lifeskim |
| pubmed-article:15536149 | lifeskim:mentions | umls-concept:C2348499 | lld:lifeskim |
| pubmed-article:15536149 | lifeskim:mentions | umls-concept:C0439677 | lld:lifeskim |
| pubmed-article:15536149 | lifeskim:mentions | umls-concept:C1511938 | lld:lifeskim |
| pubmed-article:15536149 | lifeskim:mentions | umls-concept:C1332838 | lld:lifeskim |
| pubmed-article:15536149 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:15536149 | pubmed:dateCreated | 2005-2-17 | lld:pubmed |
| pubmed-article:15536149 | pubmed:abstractText | Activating fetal liver tyrosine kinase 3 (Flt3) mutations represent the most common genetic aberrations in acute myeloid leukemia (AML). Most commonly, they occur as internal tandem duplications in the juxtamembrane domain (Flt3-ITD) that transform myeloid cells in vitro and in vivo and that induce aberrant signaling and biologic functions. We identified RGS2, a regulator of G-protein signaling, as a gene specifically repressed by Flt3-ITD. Here we demonstrate an important role of RGS2 in Flt3-ITD-mediated transformation. RGS2 was repressed after forced expression of activating Flt3 mutations in 2 myeloid cell lines (32Dcl3 and NB4). Furthermore, RGS2 was repressed in Flt3-mutation-positive AML cases in comparison to Flt3-mutation-negative cases, especially in Flt3-ITD-positive cases with a high ITD-to-wild-type (WT) ratio. Coexpression of RGS2 with Flt3-ITD inhibited Flt3-ITD-induced autonomous proliferation and clonal growth of 32D cells. RGS2 also inhibited Flt3-ITD-induced phosphorylation of Akt and glycogen synthase kinase beta (Gsk3-beta) without influencing signal transducer and activator of transcription 5 (STAT5) activation. In addition, RGS2 reinduced the expression of Flt3-ITD-repressed CCAAT/enhancer-binding protein alpha (c/EBPalpha) and antagonized the Flt3-ITD-induced differentiation block in 32D cells. Expression analyses in myeloid cell lines revealed induction of RGS2 during granulocytic but not during monocytic differentiation. Taken together, RGS2 is a novel mediator of myeloid differentiation, and its repression is an important event in Flt3-ITD-induced transformation. | lld:pubmed |
| pubmed-article:15536149 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15536149 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15536149 | pubmed:citationSubset | AIM | lld:pubmed |
| pubmed-article:15536149 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15536149 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15536149 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:15536149 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15536149 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15536149 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15536149 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15536149 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15536149 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15536149 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15536149 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15536149 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15536149 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:15536149 | pubmed:issn | 0006-4971 | lld:pubmed |
| pubmed-article:15536149 | pubmed:author | pubmed-author:BerdelWolfgan... | lld:pubmed |
| pubmed-article:15536149 | pubmed:author | pubmed-author:ThiedeChristi... | lld:pubmed |
| pubmed-article:15536149 | pubmed:author | pubmed-author:ServeHubertH | lld:pubmed |
| pubmed-article:15536149 | pubmed:author | pubmed-author:TickenbrockLa... | lld:pubmed |
| pubmed-article:15536149 | pubmed:author | pubmed-author:Müller-TidowC... | lld:pubmed |
| pubmed-article:15536149 | pubmed:author | pubmed-author:SteurClaudiaC | lld:pubmed |
| pubmed-article:15536149 | pubmed:author | pubmed-author:ChoudharyChun... | lld:pubmed |
| pubmed-article:15536149 | pubmed:author | pubmed-author:SarginBülentB | lld:pubmed |
| pubmed-article:15536149 | pubmed:author | pubmed-author:SchwäbleJoach... | lld:pubmed |
| pubmed-article:15536149 | pubmed:author | pubmed-author:BrandtsChrist... | lld:pubmed |
| pubmed-article:15536149 | pubmed:author | pubmed-author:RehageMaikeM | lld:pubmed |
| pubmed-article:15536149 | pubmed:author | pubmed-author:RudatAnnikaA | lld:pubmed |
| pubmed-article:15536149 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15536149 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:15536149 | pubmed:volume | 105 | lld:pubmed |
| pubmed-article:15536149 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15536149 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15536149 | pubmed:pagination | 2107-14 | lld:pubmed |
| pubmed-article:15536149 | pubmed:dateRevised | 2011-11-2 | lld:pubmed |
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| pubmed-article:15536149 | pubmed:meshHeading | pubmed-meshheading:15536149... | lld:pubmed |
| pubmed-article:15536149 | pubmed:year | 2005 | lld:pubmed |
| pubmed-article:15536149 | pubmed:articleTitle | RGS2 is an important target gene of Flt3-ITD mutations in AML and functions in myeloid differentiation and leukemic transformation. | lld:pubmed |
| pubmed-article:15536149 | pubmed:affiliation | Department of Medicine, Hematology, and Oncology, and the Interdisciplinary Clinical Research Center (IZKF), University Hospital Münster, Albert-Schweitzer-Strasse 33, 48129 Münster, Germany. | lld:pubmed |
| pubmed-article:15536149 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15536149 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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