HL60 is an established culture cell line of human promyelocytic leukemia cells that can be induced to differentiate terminally by a variety of chemicals. This chapter investigates the possibility that variant sublines of HL60, selected for resistance to differentiation inducers, may be useful for relating the genetic aberrations of the myeloid differentiative pathway to the leukemic phenotype. Specifically, sublines have been selected in the chapter that are resistant to three structurally unrelated inducers of neutrophilic differentiation: dimethyl sulfoxide, retinoic acid, and 6-thioguanine. Selection procedures were patterned after those effective in developing drug resistance to cytotoxic agents, most notably methotrexate, via the mechanism of amplification of the gene for the drug's cellular binding protein. However, it has been hypothesized that resistance to differentiation inducers might develop by an alternative, selectable mechanism—amplification of genes that enhance cell replication and/or decrease responsiveness to signals for terminal differentiation. Sublines resistant to retinoate and 6-thioguanine (s6G) developed numerous double minutes (unpublished), which are virtually pathognomonic for amplified genes. The Me2SO-resistant subline had neither double minutes nor chromosomal homogeneously staining regions.
|Number of pages||4|
|Journal||Progress in Nucleic Acid Research and Molecular Biology|
|State||Published - 1 Jan 1983|