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Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2002-01-0271.

Submitted January 29, 2002
Accepted July 17, 2002
Low levels of ABCG2 expression in adult AML blast samples
Brian L Abbott, Anne-Marie Colapietro, Yuxiao Barnes, Frank Marini, Michael Andreeff, and Brian P Sorrentino*
Department of Experimental Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA
Department of Molecular Hematology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
* Corresponding author; email: brian.sorrentino{at}stjude.org.
Previous reports have suggested that the ATP-binding cassette protein ABCG2 (BCRP, MXR) is associated with drug resistance in acute myeloid leukemia (AML). The aims of this study were to determine the level of ABCG2 mRNA expression necessary to produce drug resistance and to define the ABCG2 levels in normal bone marrow (BM), peripheral blood (PB), cord blood (CB), and adult AML blast cell populations. First, using transduced clonal cell lines expressing varying levels of ABCG2, we found that ABCG2 expression conferred resistance to mitoxantrone and topotecan, but not idarubicin. Next, we developed a real-time RT-PCR assay for measuring ABCG2 mRNA expression levels in clinical samples. Normal BM and PB contained low levels of ABCG2 mRNA, while higher levels were measured in CB mononuclear cells, CD34+, and Ac133+ populations, consistent with the known stem cell enrichment in these populations. Next, we studied the ABCG2 mRNA levels in 40 specimens from newly diagnosed adult AML patients. Only 7% of these samples contained ABCG2 mRNA levels within the range of our drug resistant clone, although another 78% were higher than normal blood and bone marrow. Flow cytometry revealed very small subpopulations of ABCG2-expressing cells in the cases we examined. Our data suggest that high levels of ABCG2 mRNA expression in adult AML blast specimens are relatively uncommon, and that ABCG2 expression may be limited to a small cell subpopulation in some cases.

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