title: NF-kappaB dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies.
abstract: MicroRNA miR-146a has been implicated as a negative feedback regulator of NF-κB activation. Knockout of the miR-146a gene in C57BL/6 mice leads to histologically and immunophenotypically defined myeloid sarcomas and some lymphomas. The sarcomas are transplantable to immunologically compromised hosts, showing that they are true malignancies. The animals also exhibit chronic myeloproliferation in their bone marrow. Spleen and marrow cells show increased transcription of NF-κB-regulated genes and tumors have higher nuclear p65. Genetic ablation of NF-κB p50 suppresses the myeloproliferation, showing that dysregulation of NF-κB is responsible for the myeloproliferative disease.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Jimmy L
authors.initials: JL
authors.lastname: Zhao
authors.forename: Dinesh S
authors.initials: DS
authors.lastname: Rao
authors.forename: Mark P
authors.initials: MP
authors.lastname: Boldin
authors.forename: Konstantin D
authors.initials: KD
authors.lastname: Taganov
authors.forename: Ryan M
authors.initials: RM
authors.lastname: O'Connell
authors.forename: David
authors.initials: D
authors.lastname: Baltimore
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D005838:Genotype; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D008957:Models, Genetic; D009196:Myeloproliferative Disorders / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism; D055728:Primary Myelofibrosis / Q000473:pathology; D013154:Spleen / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; D016328:NF-kappa B