Journal ArticleDOI
Identification of miR-145 and miR-146a as mediators of the 5q– syndrome phenotype
Daniel T. Starczynowski,Florian Kuchenbauer,Bob Argiropoulos,Sandy Sung,Ryan D. Morin,Andrew L Muranyi,Martin Hirst,Donna E. Hogge,Marco A. Marra,Richard A. Wells,Rena Buckstein,Wan L. Lam,R. Keith Humphries,Aly Karsan +13 more
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TLDR
Deletes chromosome 5q and identifies Toll–interleukin-1 receptor domain–containing adaptor protein (TIRAP) and tumor necrosis factor receptor–associated factor-6 (TRAF6) as respective targets of these miRNAs.Abstract:
5q- syndrome is a subtype of myelodysplastic syndrome characterized by severe anemia and variable neutropenia but normal or high platelet counts with dysplastic megakaryocytes. We examined expression of microRNAs (miRNAs) encoded on chromosome 5q as a possible cause of haploinsufficiency. We show that deletion of chromosome 5q correlates with loss of two miRNAs that are abundant in hematopoietic stem/progenitor cells (HSPCs), miR-145 and miR-146a, and we identify Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP) and tumor necrosis factor receptor-associated factor-6 (TRAF6) as respective targets of these miRNAs. TIRAP is known to lie upstream of TRAF6 in innate immune signaling. Knockdown of miR-145 and miR-146a together or enforced expression of TRAF6 in mouse HSPCs resulted in thrombocytosis, mild neutropenia and megakaryocytic dysplasia. A subset of mice transplanted with TRAF6-expressing marrow progressed either to marrow failure or acute myeloid leukemia. Thus, inappropriate activation of innate immune signals in HSPCs phenocopies several clinical features of 5q- syndrome.read more
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MicroRNAs as New Biomarkers for Diagnosis and Prognosis, and as Potential Therapeutic Targets in Acute Myeloid Leukemia.
Stefania Trino,Daniela Lamorte,Antonella Caivano,Ilaria Laurenzana,Daniela Tagliaferri,Geppino Falco,Luigi Del Vecchio,Pellegrino Musto,Luciana De Luca +8 more
TL;DR: The miRNA regulatory network in AML pathogenesis is reviewed and the potential use of cellular and circulating miRNAs as biomarkers for diagnosis and prognosis and as therapeutic targets is discussed.
Journal ArticleDOI
MicroRNAs in hematological malignancies.
TL;DR: An overview of the role and potential clinical utility for miRNAs in hematological malignancies and their function in normal hematopoiesis is provided.
Journal ArticleDOI
Genetics of Myelodysplastic Syndromes: New Insights
TL;DR: The identification of recurrent mutations in MDS samples has led to new insights into the pathophysiology of these disorders, and it is suggested that multiple mutations are required for MDS initiation and progression to acute myeloid leukemia (AML).
Journal ArticleDOI
The Administration of Escherichia coli Nissle 1917 Ameliorates Development of DSS-Induced Colitis in Mice.
Alba Rodríguez-Nogales,Francesca Algieri,José Garrido-Mesa,Teresa Vezza,M. P. Utrilla,Natalia Chueca,Jose Ángel Fernández-Caballero,Federico García,María Elena Rodríguez-Cabezas,Julio Gálvez +9 more
TL;DR: The intestinal anti-inflammatory effects of the probiotic EcN were associated with an amelioration of the altered gut microbiome in mouse experimental colitis, especially when considering bacterial diversity, which is reduced in these intestinal conditions.
Journal ArticleDOI
Overexpression of the Toll-Like Receptor (TLR) Signaling Adaptor MYD88, but Lack of Genetic Mutation, in Myelodysplastic Syndromes
Sophie Dimicoli,Yue Wei,Carlos E. Bueso-Ramos,Hui Yang,Courtney D. DiNardo,Yu Jia,Hong Zheng,Zhihong Fang,Martin Nguyen,Sherry Pierce,Rui Chen,Hui Wang,Chenghua Wu,Guillermo Garcia-Manero +13 more
TL;DR: The results indicate that MYD88 plays a role in the pathobiology of MDS and may have prognostic and therapeutic value in the management of patients with this disease.
References
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TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
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TAK1 is a ubiquitin-dependent kinase of MKK and IKK
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