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We demonstrate that a specific miR profile in bone marrow fibroblasts parallels the transition from monoclonal gammopathy of undetermined significance (MGUS) to myeloma. Overexpression of miR\u201027b\u20103p and miR\u2010214\u20103p triggers proliferation and apoptosis resistance in myeloma fibroblasts via the FBXW7 and PTEN\/AKT\/GSK3 pathways, respectively. Transient transfection of miR\u201027b\u20103p and miR\u2010214\u20103p inhibitors demonstrates a cooperation between these two miRNAs in the expression of the anti\u2010apoptotic factor MCL1, suggesting that miR\u201027b\u20103p and miR\u2010214\u20103p negatively regulate myeloma fibroblast apoptosis. Furthermore, myeloma cells modulate miR\u201027b\u20103p and miR\u2010214\u20103p expression in fibroblasts through the release of exosomes. Indeed, tumour cell\u2010derived exosomes induce an overexpression of both miRNAs in MGUS fibroblasts not through a simple transfer mechanism but by <jats:italic>de novo<\/jats:italic> synthesis triggered by the transfer of exosomal WWC2 protein that regulates the Hippo pathway. Increased levels of miR\u201027b\u20103p and miR\u2010214\u20103p in MGUS fibroblasts co\u2010cultured with myeloma cell\u2010derived exosomes enhance the expression of fibroblast activation markers \u03b1SMA and FAP. These data show that the MGUS\u2010to\u2010myeloma transition entails an aberrant miRNA profile in marrow fibroblasts and highlight a key role of myeloma cells in modifying the bone marrow microenvironment by reprogramming the marrow fibroblasts' behaviour. Copyright \u00a9 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.5187","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T05:16:11Z","timestamp":1540444571000},"page":"241-253","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Bone marrow fibroblasts overexpress miR\u201027b and miR\u2010214 in step with multiple myeloma progression, dependent on tumour cell\u2010derived exosomes"],"prefix":"10.1002","volume":"247","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4720-3393","authenticated-orcid":false,"given":"Maria Antonia","family":"Frassanito","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Unit of General Pathology University of Bari Aldo Moro Medical School  Bari 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