| pubmed-article:21076613 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21076613 | lifeskim:mentions | umls-concept:C0023467 | lld:lifeskim |
| pubmed-article:21076613 | lifeskim:mentions | umls-concept:C0212320 | lld:lifeskim |
| pubmed-article:21076613 | lifeskim:mentions | umls-concept:C1101610 | lld:lifeskim |
| pubmed-article:21076613 | lifeskim:mentions | umls-concept:C0013081 | lld:lifeskim |
| pubmed-article:21076613 | lifeskim:mentions | umls-concept:C1711351 | lld:lifeskim |
| pubmed-article:21076613 | pubmed:issue | 11 | lld:pubmed |
| pubmed-article:21076613 | pubmed:dateCreated | 2010-11-15 | lld:pubmed |
| pubmed-article:21076613 | pubmed:abstractText | Core-binding factor leukemia (CBFL) is a subgroup of acute myeloid leukemia (AML) characterized by genetic mutations involving the subunits of the core-binding factor (CBF). The leukemogenesis model for CBFL posits that one, or more, gene mutations inducing increased cell proliferation and/or inhibition of apoptosis cooperate with CBF mutations for leukemia development. One of the most common mutations associated with CBF mutations involves the KIT receptor. A high expression of KIT is a hallmark of a high proportion of CBFL. Previous studies indicate that microRNA (MIR) 222/221 targets the 3' untranslated region of the KIT messenger RNA and our observation that AML1 can bind the MIR-222/221 promoter, we hypothesized that MIR-222/221 represents the link between CBF and KIT. Here, we show that MIR-222/221 expression is upregulated after myeloid differentiation of normal bone marrow AC133(+) stem progenitor cells. CBFL blasts with either t(8;21) or inv(16) CBF rearrangements with high expression levels of KIT (CD117) display a significantly lower level of MIR-222/221 expression than non-CBFL blasts. Consistently, we found that the t(8;21) AML1-MTG8 fusion protein binds the MIR-222/221 promoter and induces transcriptional repression of a MIR-222/221-LUC reporter. Because of the highly conserved sequence homology, we demonstrated concomitant MIR-222/221 down-regulation and KIT up-regulation in the 32D/WT1 mouse cell model carrying the AML1-MTG16 fusion protein. This study provides the first hint that CBFL-associated fusion proteins may lead to up-regulation of the KIT receptor by down-regulating MIR-222/221, thus explaining the concomitant occurrence of CBF genetic rearrangements and overexpression of wild type or mutant KIT in AML. | lld:pubmed |
| pubmed-article:21076613 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21076613 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21076613 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:21076613 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21076613 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21076613 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21076613 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21076613 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21076613 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21076613 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21076613 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21076613 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:21076613 | pubmed:issn | 1476-5586 | lld:pubmed |
| pubmed-article:21076613 | pubmed:author | pubmed-author:MorraEnricaE | lld:pubmed |
| pubmed-article:21076613 | pubmed:author | pubmed-author:SacchiNicolet... | lld:pubmed |
| pubmed-article:21076613 | pubmed:author | pubmed-author:CairoliRobert... | lld:pubmed |
| pubmed-article:21076613 | pubmed:author | pubmed-author:BeghiniAlessa... | lld:pubmed |
| pubmed-article:21076613 | pubmed:author | pubmed-author:RossettiStefa... | lld:pubmed |
| pubmed-article:21076613 | pubmed:author | pubmed-author:PezzettiLaura... | lld:pubmed |
| pubmed-article:21076613 | pubmed:author | pubmed-author:NichelattiMic... | lld:pubmed |
| pubmed-article:21076613 | pubmed:author | pubmed-author:ScarpatiBarba... | lld:pubmed |
| pubmed-article:21076613 | pubmed:author | pubmed-author:TurriniMauroM | lld:pubmed |
| pubmed-article:21076613 | pubmed:author | pubmed-author:FischerJohnJ | lld:pubmed |
| pubmed-article:21076613 | pubmed:author | pubmed-author:CorlazzoliFra... | lld:pubmed |
| pubmed-article:21076613 | pubmed:author | pubmed-author:BrioschiMatte... | lld:pubmed |
| pubmed-article:21076613 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21076613 | pubmed:volume | 12 | lld:pubmed |
| pubmed-article:21076613 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21076613 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21076613 | pubmed:pagination | 866-76 | lld:pubmed |
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| pubmed-article:21076613 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:21076613 | pubmed:articleTitle | Down-regulation of microRNAs 222/221 in acute myelogenous leukemia with deranged core-binding factor subunits. | lld:pubmed |
| pubmed-article:21076613 | pubmed:affiliation | Dipartimento di Biologia e Genetica per le Scienze Mediche, Facoltà di Medicina, Università degli Studi di Milano, Milan, Italy. | lld:pubmed |
| pubmed-article:21076613 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21076613 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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