The R-Smad-Smad 4 complex cooperates with sequence-specific transcription factors such as ymphoid enhancer-binding factor 1/T cell factor (LEF1/TCF), ymphoid enhancer-binding factor 1/T cell factor (LEF1/TCF), core-binding factor A/acute myeloneous leukemia (CBFA/AML) and the coactivators CREB-binding protein (CBP) or p300 to activate transcription in response to TGF-β ligand (Derynck and Zhang, 2003), thus affecting osteoblast proliferation, differentiation, and type I collagen synthesis (Runyan et al., 2012; Ota et al., 2013; Li et al., 2015). The gene discussed is CREBBP; the disease is acute myeloid leukemia.