Among these factors, it has been recently proven, by means of in vitro and in vivo assays, that B-ALL-derived TNFα can activate NF-kB downstream of tumor necrosis factor receptor 1 (TNFR1) on MSCs, and possibly on other cell subsets within the BM niche, resulting for example in matrix metallopeptidase 9 (MMP-9) secretion [130]. Here, TNF is linked to precursor B-cell acute lymphoblastic leukemia.