Here, induction of osteogenesis was ascribed to activation of Smad-1/5 signaling in MSCs by bone morphogenetic proteins (BMPs) derived from AML cells and to overexpression of connective tissue growth factor (CTGF) in MSCs, leading to an increase of pre-osteoblastic cells in the leukemic niche that enhances AML expansion [153]. This evidence concerns the gene SMAD1 and acute myeloid leukemia.