Transforming growth factor β: Possible roles in the regulation of normal and leukemic hematopoietic cell growth

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Abstract
We have recently demonstrated that transforming growth factor (TGF)‐β1 and TGF‐β2 are potent inhibitors of the growth and differentiation of murine and human hematopoietic cells. The proliferation of primary unfractionated murine bone marrow by interleukin‐3 (IL‐3) and human bone marrow by IL‐3 or granulocyte/macrophage colony‐stimulating factor (GM‐CSF) was inhibited by TGF‐β1 and TGF‐β2, while the proliferation of murine bone marrow by GM‐CSF or murine and human marrow with G‐CSF was not inhibited. Mouse and human hematopoietic colony formation was differentially affected by TGF‐β1. In particular, CFU‐GM, CFU‐GEMM, BFU‐E, and HPP‐CFC, the most immature colonies, were inhibited by TGF‐β1, whereas the more differentiated unipotent CFU‐G, CFU‐M, and CFU‐E were not affected. TGF‐β1 inhibited IL‐3‐induced growth of murine leukemic cell lines within 24 h, after which the cells were still viable. Subsequent removal of the TGF‐β1 results in the resumption of normal growth. TGF‐β1 inhibited the growth of factor‐dependent NFS‐60 cells in a dose‐dependent manner in response to IL‐3, GM‐CSF, G‐CSF, CSF‐1, IL‐4, or IL‐6. TGF‐β1 inhibited the growth of a variety of murine and human myeloid leukemias, while erythorid and macrophage leukemias were insensitive. Lymphoid leukemias, whose normal cellular counterparts were markedly inhibited by TGF‐β, were also resistant to TGF‐β1 inhibition. These leukemic cells have no detectable TGF‐β1 receptors on their cell surface. Last, TGF‐β1 directly inhibited the growth of isolated Thy‐1‐positive progenitor cells. Thus, TGF‐β may be an important modulator of normal and leukemic hematopoietic cell growth.