OBJECTIVE: Human acute myeloid leukemia (AML) cells can proliferate in vitro in the absence of added growth factors when cultured at high cell density. Autocrine growth factor production is a postulated mechanism of autonomous growth. We sought to examine this using murine AML cells. MATERIALS AND METHODS: We have utilized a Moloney murine leukemia virus (M-MuLV) model of AML to investigate the nature of autonomous in vitro growth of myeloid leukemic cells. RESULTS: Like human AML, M-MuLV-induced myeloid leukemic cells displayed autonomous growth in unstimulated high cell density cultures. However, replating of individual, primary, growth factor autonomous colonies of leukemic cells demonstrated the presence of clonogenic cells capable of autonomous growth when cultured at low cell density. In addition, there was heterogeneity in the progeny of these cells: both factor-dependent leukemic cells and cells autonomous of exogenous factor were observed. CONCLUSION: We propose that clonogenic cells capable of autonomous growth at low cell density represent leukemic progenitors while the majority of leukemic cells derived from these "autonomous" leukemic cells are factor-dependent.
OBJECTIVE:Humanacute myeloid leukemia (AML) cells can proliferate in vitro in the absence of added growth factors when cultured at high cell density. Autocrine growth factor production is a postulated mechanism of autonomous growth. We sought to examine this using murineAML cells. MATERIALS AND METHODS: We have utilized a Moloney murine leukemia virus (M-MuLV) model of AML to investigate the nature of autonomous in vitro growth of myeloid leukemic cells. RESULTS: Like humanAML, M-MuLV-induced myeloid leukemic cells displayed autonomous growth in unstimulated high cell density cultures. However, replating of individual, primary, growth factor autonomous colonies of leukemic cells demonstrated the presence of clonogenic cells capable of autonomous growth when cultured at low cell density. In addition, there was heterogeneity in the progeny of these cells: both factor-dependent leukemic cells and cells autonomous of exogenous factor were observed. CONCLUSION: We propose that clonogenic cells capable of autonomous growth at low cell density represent leukemic progenitors while the majority of leukemic cells derived from these "autonomous" leukemic cells are factor-dependent.