Low levels of ABCG2 expression in adult AML blast samples
- 15 December 2002
- journal article
- Published by American Society of Hematology in Blood
- Vol. 100 (13), 4594-4601
- https://doi.org/10.1182/blood-2002-01-0271
Abstract
Previous reports have suggested that the adenosine triphosphate–binding cassette protein ABCG2 (breast cancer resistance protein [BCRP], mitoxantrone resistance [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 to idarubicin. Next, we developed a real-time reverse transcription–polymerase chain reaction 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.Keywords
This publication has 15 references indexed in Scilit:
- The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitorsBlood, 2002
- Breast cancer resistance protein expression and resistance to daunorubicin in blast cells from patients with acute myeloid leukaemiaBritish Journal of Haematology, 2001
- The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotypeNature Medicine, 2001
- A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemiaBlood, 2001
- Expression of breast cancer resistance protein in blast cells from patients with acute leukemiaBlood, 2000
- A multidrug resistance transporter from human MCF-7 breast cancer cellsProceedings of the National Academy of Sciences of the United States of America, 1998
- Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple speciesNature Medicine, 1997
- P-Glycoprotein Expression in De Novo Acute Myeloid LeukemiaLeukemia & Lymphoma, 1997
- Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.The Journal of Experimental Medicine, 1996
- Expression of a full-length cDNA for the human "MDR1" gene confers resistance to colchicine, doxorubicin, and vinblastine.Proceedings of the National Academy of Sciences of the United States of America, 1987