Role of Biologic Response Modifiers in the Growth and Differentiation of Myeloid Leukemic Cells

Human myeloid leukemic cells usually fail to grow or differentiate in vitro. The ability of cytokines to stimulate leukemic cell proliferation was first shown in well-differentiated T-cell leukemias using interleukin-2 (Poiesz et al., 1980). However, the role of hematopoietic growth factors in the initiation or progression of myeloid leukemic cells is not clear. A small fraction of almost all human myeloid leukemic cells show a proliferate response to one of these growth factors-IL-1, IL-3, CSF-1 GM-CSF or G-CSF (Griffin et al., 1986; Pebusque et al., 1988). These responding cells usually undergo terminal differentiation and cease cell proliferation. In rare cases, permanent cell lines which are usually factor independent can be established (Ferraro and Rovera, 1984). The question of why these hematopoietic growth factors can not control the growth and differentiation of leukemic cells remains unanswered. Making the assumption that the ability of these factors to transduce the correct biochemical signals was compromised in these cells, we asked whether differentiation signals that bypassed the cell membrane could stimulate terminal differentiation. In addition, since loss of responsiveness to growth inhibitors such as TGF-3 has been proposed to contribute to neoplastic growth of various cell types, we examined the role of TGF-3 in myeloid leukemic growth.