Cholesterol synthesis and import contribute to protective cholesterol increments in acute myeloid leukemia cells

Deborah E. Banker, Sasha J. Mayer, Henry Y. Li, Cheryl L. Willman, Frederick R. Appelbaum, Richard A. Zager

Research output: Contribution to journalArticlepeer-review

Abstract

Cholesterol levels are abnormally increased in many acute myeloid leukemia (AML) samples exposed In vitro to chemotherapy. Blocking these acute cholesterol responses selectively sensitises AML cells to therapeutics. Thus, defining the molecular mechanisms by which AML cells accomplish these protective cholesterol increments might elucidate novel therapeutic targets. We now report that the levels of mRNAS encoding the cholesterol synthesis-regulating enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and the cholesterol-importing low-density lipoprotein (LDL) receptor were both increased by daunorubicin (DNR) or cytarabine (ARA-C) treatments in almost three fourths of cultured AML samples. However, less than one third of AML samples significantly increased LDL accumulation during drug treatments, suggesting that de novo synthesis is the primary mechanism by which most AML cells increase cholesterol levels during drug exposures. LDL increments were not correlated with cholesterol increments in ARA-C-treated AML samples. However, LDL and cholesterol increments did correlate in DMR-treated AML samples where they were measured, suggesting that a subset of AMLs may rely on increased LDL accumulation during treatment with particular drugs. Our data suggest that cholesterol synthesis inhibitors may improve the efficacy of standard antileukemia regimens, but that for maximum benefit, therapy may need to be tailored for individual patients with leukemia.

Original languageEnglish (US)
Pages (from-to)1816-1824
Number of pages9
JournalBlood
Volume104
Issue number6
DOIs
StatePublished - Sep 15 2004

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Cholesterol synthesis and import contribute to protective cholesterol increments in acute myeloid leukemia cells'. Together they form a unique fingerprint.

Cite this