Tumour promoting functions of TGF-β in CML-initiating cells.

Recent data have shown that transforming growth factor-β (TGF-β) plays bi-directional roles in the maintenance of cancer stem cells in a cell-type and context-dependent manner. Zhu et al. (TGF-β1-induced PI3K/Akt/NF-κB/MMP9 signalling pathway is activated in Philadelphia chromosome-positive chronic myeloid leukaemia hemangioblasts. J. Biochem. 2011;149:405-414) studied the functions of TGF-β in hemangioblasts from patients with chronic myeloid leukemia (CML), which displayed properties of leukemia-initiating cells. They have shown that the BCR/ABL oncoprotein induced the production of TGF-β in the CML hemangioblasts, and that TGF-β activated the phosphoinositide 3-kinase-Akt-NF-κB pathway in these cells. Activation of this pathway enhanced the production of matrix metalloproteinase-9 leading to increased synthesis of soluble Kit ligand and intercellular adhesion molecule-1. TGF-β is known to maintain the CML-initiating cells through the Akt-FoxO pathway. Together, these findings suggest that TGF-β may exhibit multiple functions in progression of CML through acting on leukemia-initiating cells.