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Switch in Differentiative Response to Maturation Inducers of Human Promyelocytic Leukemia Cells by Prior Exposure to Alkaline Conditions¹

University of Maryland Cancer Center, and Departments of Pathology and Medicine, University of Maryland, School of Medicine, Baltimore, Maryland 21201

The myeloid lineage to which HL-60 promyelocytic leukemia cells will differentiate in response to a chemical differentiation inducer can be switched by altering the pH of the growth medium. Cells passaged previously at pH 7.2 become neutrophiles, and those passaged previously at pH 7.6 become eosinophiles after 5 to 7 days of culture in the presence of 0.5 mM butyric acid. Butyric acid and its analogues are unique in that all other chemical maturation inducers tested, such as dimethyl sulfoxide and retinoic acid, promote neutrophilic differentiation regardless of the prior culture history of the cells. This suggests that lineage commitment and maturational commitment are mechanistically separate processes in this multipotential cell line and can be independently manipulated experimentally.

¹ This work was supported in part by grants from the Vicki Via Dotson Memorial Leukemia Foundation, American Cancer Society Institutional Grant IN-174A, and the American Cancer Society, Maryland Division, Inc.

² To whom requests for reprints should be addressed.

Received 10/17/84. Revised 1/18/85. Accepted 1/30/85.