Differentiation induction in myeloid leukemic cells.

Work based on immortalised leukemic cell lines indicates that the maturation arrest in leukemia can be reversible. Successful differentiation induction would mean restoring the link between proliferation and differentiation. Human cell lines such as the promyelocytic HL-60 and the monoblastic U-937 can be induced to mature by incubation with a wide variety of agents, e.g. phorbol diesters, retinoic acid and 1,25-dihydroxycholecalciferol. In addition, mitogen-stimulated lymphocytes and some T-lymphocyte lines produce a polypeptide called the differentiation-inducing factor (DIF), which mediates maturation of HL-60 into macrophage-like cells with resulting proliferation inhibition. DIF also displays a primary growth inhibitory effect on certain subclones of the cell lines as well as on fresh clonogenic cells from patients with acute myeloid leukemia and on normal granulocyte-macrophage progenitors. Our data indicate that there is more than one way to induce differentiation in leukemia but final common pathways may exist. Complementary, synergistic, maturation effects are seen between some agents, which may become of clinical utility.