SMAD4 and acute myeloid leukemia: One major mechanism to resist the cytostatic effect of TGF-β is through frequent inactivating mutations and deletions in Smad4/DPC4 in gastrointestinal and pancreatic cancer.32 Although a few mutations or deletions of Smad4 have been reported to attenuate TGF-β-mediated signaling in AML, genetic mutations in Smad4 are rare events in leukemia.