کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151909 | 1090032 | 2010 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Down-regulation of MicroRNAs 222/221 in Acute Myelogenous Leukemia with Deranged Core-Binding Factor Subunits
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کلمات کلیدی
EPOGM-CSFBM-MNCBFU-ECFU-GMAMLgranulocyte/macrophage colony-stimulating factor - granulocyte / ماکروفاژ عامل کلونی تحریک کنندهHSPCs - HSPC هاerythropoietin - اریتروپویتینBone marrow mononuclear cells - سلول های تک هسته ای مغز استخوانHematopoietic stem/progenitor cells - سلولهای بنیادی / پروتئین هماتوپوئیتgranulocyte colony-stimulating factor - فاکتور تحریک کننده کلنی گرانولوسیتG-CSF - فاکتور محرک کُلونی گرانولوسیتacute myeloid leukemia - لوسمی حاد میلوئیدی یا به اختصار AMLerythroid burst-forming units - واحدهای پاره شدن اریترویید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Core-binding factor leukemia (CBFL) is a subgroup of acutemyeloid 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 commonmutations 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 3â² 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 12, Issue 11, November 2010, Pages 866-876, IN2-IN3
Journal: Neoplasia - Volume 12, Issue 11, November 2010, Pages 866-876, IN2-IN3
نویسندگان
Matteo Brioschi, John Fischer, Roberto Cairoli, Stefano Rossetti, Laura Pezzetti, Michele Nichelatti, Mauro Turrini, Francesca Corlazzoli, Barbara Scarpati, Enrica Morra, Nicoletta Sacchi, Alessandro Beghini,