This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Madden, E. A. Articles by Melnykovych, G. Search for Related Content PubMed PubMed Citation Articles by Madden, E. A. Articles by Melnykovych, G.

Possible Role of Cholesterol in the Susceptibility of a Human Acute Lymphoblastic Leukemia Cell Line to Dexamethasone¹

Research Service 151, Veterans Administration Medical Center, Kansas City, Missouri 64128 [A. M. F., G. M.], and Department of Microbiology, Kansas University Medical Center, Kansas City, Kansas 66103 [E. J. B., A. M. F., G. M.]

Because the absence of high affinity glucocorticoid receptors in lymphoid leukemia cells does not always correlate with the resistance to glucocorticoids in vitro, an effort was made to identify an alternate biochemical marker which, independently from the receptor system, would improve the reliability of the existing in vitro sensitivity assays as predictors of the patients' response to glucocorticoid therapy. Two receptor-containing lines of acute lymphoblastic leukemia, one glucocorticoid sensitive (CEM-C7) and one glucocorticoid resistant (CEM-C1), were used to study endogenous synthesis of cholesterol with [¹⁴C]-acetate as a cholesterol precursor. We found that dexamethasone inhibited cholesterol synthesis in the glucocorticoid-sensitive clone but was without effect on the resistant clone. In sensitive cells, this reduction in synthesis was paralleled by a decreased activity of 3-hydroxy-3-methylglutaryl coenzyme A synthase (EC 1.1.3.5) and was followed by a moderate decrease in cellular free cholesterol. Moreover, sonic dispersions of cholesterol in delipidized serum when added to the cultures reversed the growth-inhibitory effect of dexamethasone on CEM-C7 cells.

¹ Supported by NIH Grant CA-08315 and by the Veterans Administration (Project No. 5662-01).

² Present address: Department of Biochemistry and Nutrition, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.

³ To whom requests for reprints should be addressed.

Received 6/17/85. Revised 10/ 4/85. Accepted 10/11/85.

This article has been cited by other articles:

				J. D. Smith, M. Miyata, M. Ginsberg, C. Grigaux, E. Shmookler, and A. S. Plump Cyclic AMP Induces Apolipoprotein E Binding Activity and Promotes Cholesterol Efflux from a Macrophage Cell Line to Apolipoprotein Acceptors J. Biol. Chem., November 29, 1996; 271(48): 30647 - 30655. [Abstract] [Full Text] [PDF]