Transforming growth factorβ inhibits growth of more differentiated myeloid leukemia cells and retinoblastoma protein phosphorylation at serine 795

Transforming growth factor beta (TGF-beta) has been shown to be a specific inhibitor of early human myeloid progenitors. me show here that TGF-beta 1 potentially inhibited not only the growth of primitive but also more mature myeloid leukemic cells. Surprisingly, those apparently more mature progenitor cells, such as MV4-11 and Mo7e cells, are very sensitive to the action of TGF-beta. The addition of TGF-beta 1 to liquid cultures of these cells significantly inhibited their proliferation, with as much as 72% inhibition of growth of MV4-11 cells. The suppressive effect by TGF-beta 1 was not reversed or prevented by granulocyte-macrophage colony-stimulating factor or interleukin 3 used to promote cell growth in TF-1a and MIV4-11 cells. TGF-beta 1 completely abolished the clonal growth of MV4-11 cells in soft agar and inhibited Mo7e, KG-1, K562, TF-1, and TF-la colony growth by 99%, 90%, 63%, 53%, and 43%, respectively. The cells treated with TGF-beta 1 showed progressive accumulation in the G1 phase of cell cycle. Maximal G1 arrest (93%) was observed in MV4-11 cells. Using anti-retinoblastoma protein (pRb) and anti-specific phosphorylated-pRb antibodies, me demonstrated that TGF-beta 1 greatly inhibited pRb phosphorylation at serine 795 in MV4-11 and Mo7e cells. Taken together, our data suggest that the sensitivity of myeloid leukemic progenitor cells to growth inhibition by TGF-beta may not be inversely correlated with their maturation stage, and the inhibition of the cells appeared to be linked to the suppression of pRb phosphorylation at serine 795. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.