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-receptor-alpha (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.


CONCLUSIONS
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.
Peeters
Susan D P W M
SD
Department of Hematology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
van der Kolk
Dorina M
DM
de Haan
Gerald
G
Bystrykh
Leonid
L
Kuipers
Folkert
F
de Vries
Elisabeth G E
EG
Vellenga
Edo
E
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis*; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000208:Acute Disease; D018952:Antigens, CD34 / Q000032:analysis*; D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D018528:ATP-Binding Cassette Transporters; D018952:Antigens, CD34; D017931:DNA Primers; D002784:Cholesterol; D051997:ADP-ribosyl Cyclase 1