Low levels of ABCG2 expression in adult AML blast samples
Low levels of ABCG2 expression in adult AML blast samples
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DOI：
10.1182/blood-2002-01-0271
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发表时间：
2002-12-15
期刊：
影响因子：
20.3
通讯作者：
Sorrentino, BP
中科院分区：
文献类型：
--
作者：
Abbott, BL;Colapietro, AM;Sorrentino, BP
以前的报道表明，三磷酸腺苷结合盒蛋白ABCG 2（乳腺癌耐药蛋白[BCRP]、米托蒽醌耐药[MXR]）与急性髓系白血病（AML）的耐药相关;本研究的目的是确定产生耐药性所必需的ABCG 2 mRNA表达水平，并确定正常骨髓（BM）、外周血（PB）、骨髓基质细胞（BM）和骨髓基质细胞（BM）中的ABCG 2水平。脐带血（CB）和成人AML母细胞群。首先，使用表达不同水平ABCG 2的转导克隆细胞系，我们发现ABCG 2表达赋予对米托蒽醌和拓扑替康的抗性，但不赋予对依达罗的抗性。接下来，我们开发了一种实时逆转录-聚合酶链反应测定临床样本中ABCG 2 mRNA的表达水平。正常BM和PB含有低水平的ABCG 2 mRNA，而在CB单核细胞、CD 34（+）和Ac 133（+）群体中测量到较高水平的ABCG 2 mRNA，这与这些群体中已知的干细胞富集一致。接下来，我们研究了来自新诊断的成人AML患者的40个样本中的ABCG 2 mRNA水平。这些样本中只有7%的ABCG 2 mRNA水平在我们的耐药克隆的范围内，尽管另外78%高于正常血液和骨髓。流式细胞术显示在我们检查的病例中ABCG 2表达细胞的亚群非常小。我们的数据表明，成人AML原始细胞标本中ABCG 2 mRNA的高水平表达相对罕见，在某些情况下，ABCG 2表达可能仅限于小细胞亚群。
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 It hat 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.