Induction of Differentiation of Human Promyelocytic Leukemia Cells (HL-60) by Nucleosides and Methotrexate

Abstract

Various purine and pyrimidine analogs and methotrexate were tested to determine whether they induce morphologic and functional myeloid differentiation in HL-60, a human promyelocytic leukemia cell line. Functional maturity was assessed by nitro blue tetrazolium reduction assays. 3-Deazauridine caused nearly all of the cells to differentiate during 6 days of treatment. Pyrazofurin, virazole, puromycin aminonucleoside, and the tricyclic nucleoside 3-amino-1,5-dihydro-5-methyl-1-β-d-ribofuranosyl-1,4,5,6,8-pentaazaacenaphthylene induced maturation in 44–64% of the cells, whereas 5-azacytidine, 5-bromo-2′-deoxyuridine, 5-iodo-2′-deoxyuridine, thymidine, and the antimetabolite methotrexate induced maturation in 28–36% of the cells. In terms of effective concentration, the most potent inducer was methotrexate (10⁻⁸M). The predominant cell types after treatment with all of these compounds were the metamyelocyte and banded neutrophilic granulocyte.