NF-κB dysregulation in microRNA-146a–deficient mice drives the development of myeloid malignancies
Menée sur un modèle murin dépourvu du gène du micro-ARN 146-a, cette étude montre que la dérégulation de la voie de signalisation NF-kappaB est responsable du développement d'une maladie myéloproliférative
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.