BioProject

Primary Myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megakaryopoiesis and myelofibrosis. More...

Primary Myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megakaryopoiesis and myelofibrosis. Through a gene expression profile (GEP) study we recently highlighted the MAF upregulation in PMF versus healthy donor (HD) CD34+ hematopoietic progenitor cells (HPCs). To shed some light into the role of MAF in PMF pathogenesis, here we unravelled the effects of the overexpression of MAF in HPCs forcing its expression in HPCs. We showed that MAF overexpression favours the megakaryocyte and monocyte/macrophage commitment and leads to the abnormal expression of genes coding for proinflammatory and profibrotic mediators. Due to the key role of the above-mentioned processes in PMF pathogenesis, we selected a subset of genes coding for secreted molecules for further validation by quantitative enzyme-linked immunoassays. Noteworthy, our data unveiled a causal connection between the upregulation of MAF and the increased plasma levels of key proinflammatory/profibrotic mediators (IL8, CCL2, PLAUR and MMP9) in PMF patients. Similarly, the upregulation of MAF was responsible for the deranged expression of LGALS3 and SPP1, that are profibrotic mediators increased in PMF patients compared with HDs. Overall design: RNA from CD34+ HPCs retrovirally transduced to overexpress either the MAF splicing variant 1 (RefSeq NM_005360.3) or the MAF variant 2 (RefSeq NM_001031804.1). RNA was collected from a set of 3 independent experiments. Less...