Reversibility of Vitamin D-Induced Human Leukemia Cell-Line Maturation*

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Abstract
HL-60 cells are induced to differentiate along a monocytic pathway by the active metabolites of vitamin D3, e.g. 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. All such differentiated cells share a number of features in common but are heterogeneous in their ability to adhere to solid substrates and to resorb devitalized bone matrix. Here, we show that, in addition, as compared to the nonadherent, adherent cells are smaller, less likely to be in the S phase, more enriched in the human monocyte-specific cell surface antigen, 63D3, and contain less cmyc messenger RNA (mRNA). In addition, we document that removal of the hormone leads to dedifferentiation. For these susceptible mononuclear cells, removal of 1,25-(OH)2D3 results in a reversion to a more myeloblastic phenotype, renewed cell proliferation, and the rapid appearance of elevated levels of cmyc mRNA. Finally, we report that the cells that do not revert upon 1,25-(OH)2D3 removal are those that became multinucleated during treatment.