Interestingly, Rubio et al. showed that loss of TP53 and RB in osteogenic progenitors derived from murine BM-MSCs, but not ASCs, resulted in the formation of metastatic osteosarcoma.139 Additionally, leiomyosarcoma-like tumors were promoted in TP53 and RB null undifferentiated BM-MSCs or ASCs.139 Together these observations suggest that not only is a certain level of osteogenic differentiation required for osteosarcoma development but that the source of the cells of the osteogenic lineage is also important. This evidence concerns the gene RB1 and osteosarcoma.