Loss of irreversibility of granulocytic differentiation induced by dimethyl sulfoxide in HL-60 sublines with a homogeneously staining region.

The human HL-60 acute leukemia cell line harbors double minutes (dmins) during early passages. During its continuous culture for a long term, a single marker chromosome with a homogeneously staining region (HSR) replaces the dmins. The both structures harbor amplified c-MYC sequences. Here we ask how the cellular phenotype is altered by the c-MYC integration into a HSR. Treatment with dimethyl sulfoxide induces granulocytic differentiation in the both types of cells. In contrast to HL-60/dmin cells, however, no apoptosis followed differentiation and the differentiation phenotype was reverted upon withdrawal of the drug in HL-60/HSR cells. Terminal differentiation and loss of DNase I hypersensitivity sites at c-MYC P2 promoter appeared to be unlinked in the both types of cells. By comparison with HL-60/dmin cells, we conclude that the integration into a HSR of an extrachromosomal gene(s) but not c-MYC likely leads to the loss of irreversibility of the differentiation phenotype. Copyright 2001 Academic Press.