SMAD4 and neoplasm: Smad4 as a tumor suppressor was a binding partner of HOXA9, Quéré et al. found that HOXA9 interacted with Smad4 in the cytoplasmic and protected the transformation of normal HSPCs induced by HOXA9, and ruined their interaction with truncated Smad4 leads to the increasing of its target genes such as p15, p21, p27, activates the TGF-β signaling pathway and induces apoptosis in leukemic stem cells(LSCs) [72].