Selective expression of cholesterol metabolism genes in normal CD34(+)CD38(-) cells with a heterogeneous expression pattern in AML cells

Objective. To identify adenosine triphosphate-binding-cassette (ABC) transporters that are selectively expressed in normal and/or leukemic CD34(+)CD38(-) stem cells. Methods. Microarray experiments on murine stem cells identified 13 ABC transporters with a high expression level. Corresponding human transporters were analyzed in normal CD34(+)CD38(-) and CD34(+)CD38(+) bone marrow cells by quantitative reverse transcriptase polymerase chain reaction.

Results. Five ABC transporters, including ABCG1, were differentially expressed with a higher expression in CD34(+)CD38(-) cells. Besides ABCG1, known to be involved in cholesterol metabolism, expression of another major cholesterol transporter (ABCA1), some cholesterol metabolism genes (3-hydroxy-3-methyl-glutaryl-CoA reductase, low-density lipoprotein receptor), and the transcription factor controlling ABCA1 and ABCG1 expression, liver-X-receptoralpha (LXR-alpha), were assessed. All these genes were predominantly expressed in the more primitive subpopulation, indicating a high rate of cholesterol metabolism and transport. Conversely in acute myeloid leukemia (AML), a heterogeneous expression pattern was found consisting of a considerably higher expression of particularly LXR-alpha in CD34(+) cells and a reverse expression pattern in a subset of AML CD34(+)CD38(+) cells.

Conclusion. These data suggest an active cholesterol metabolism and efflux in normal CD34(+)CD38(-) cells, although a subgroup of AMLs potentially demonstrate a hyperactive cholesterol metabolism. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.