Leukemic cell maturation: variability of the myeloid leukemic cell phenotype

Leukemia is characterized by a proliferation of cells that exhibit an arrest in the normal differentiation sequence. The HL-60 promyelocytic leukemia is a useful model of the phenomenon of maturation arrest, particularly as modulated by inducers that partially restore myeloid differentiation. In this investigation, we report the development of two sublines of HL-60 and the acquisition of two others that are clonal variants of the parent cell line. Each of the sublines demonstrates an altered pattern of differentiation and resistance to one or more of the drugs that serves as an inducer of the parent line. The two cell lines developed in this study, HL-60S and HL-60I, are resistant to arabinosylcytocine (ARA-c); HL-60I is also resistant to PMA. A study of the phenotype as expressed by the granule-associated cytoplasmic enzymes revealed that each subline had a slightly different pattern of maturation in response to dimethylsulfoxide (DMSO) or ARA-c as inducers. The proliferative rate of all sublines was similar. These data demonstrate that the maturation arrest observed in this model is in part reversible. The maturation arrest observed in myeloid leukemias is due to a reversible block secondary to altered proliferative activity.