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.
Kitajima
K
K
Life Science Group, Faculty of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8521, Japan.
Haque
M
M
Nakamura
H
H
Hirano
T
T
Utiyama
H
H
D000208:Acute Disease; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002467:Cell Nucleus / Q000235:genetics / Q000648:ultrastructure; D002843:Chromatin / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005784:Gene Amplification; D016259:Genes, myc; D005819:Genetic Markers; D006098:Granulocytes / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007700:Kinetics; D007951:Leukemia, Myeloid / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis
D002843:Chromatin; D005819:Genetic Markers; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D004121:Dimethyl Sulfoxide