Factors inhibiting differentiation of myeloid leukemia cells

Leukemic cells are arrested in less differentiated stages of development. However, there are many reports that various leukemic cells can be induced to differentiate into mature cells with attenuation of proliferative and leukemogenic activity. Mouse myeloid leukemia (Ml) cells both in vitro and in vivo can be induced to differentiate into macrophages and granulocytes by various compounds. During long-term culture of Ml cells, however, some populations of the cells spontaneously become resistant to induces of cell differentiation. The isolated resistant variant cell lines have higher leukemogenicity than parent cells and produce differentiation inhibitory protein factors (I-factor). The variant cell lines are useful to studies on how leukemic cells are arrested in less differentiated stages even in the presence of differentiation inducers both in vitro and in vivo. We have purified and characterized the I-factor. We review herein the properties of the I-factor and other inhibitory factors of differentiation of myeloid leukemia cells.