Defective transport is a common mechanism of acquired methotrexate resistance in acute lymphocytic leukemia and is associated with decreased reduced folate carrier expression
Defective transport is a common mechanism of acquired methotrexate resistance in acute lymphocytic leukemia and is associated with decreased reduced folate carrier expression
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DOI：
10.1182/blood.v89.3.1013
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发表时间：
1997-02-01
期刊：
影响因子：
20.3
通讯作者：
Bertino, JR
中科院分区：
文献类型：
--
作者：
Gorlick, R;Goker, E;Bertino, JR
用荧光MTX类似物(PT430)置换试验(血液80：1158,1992)检测了27例初治急性淋巴细胞白血病(ALL)患者和31例复发ALL患者的MTX转运。只有13%的未经治疗的患者被认为MTX转运受损，而超过70%的复发患者有MTX转运受损的证据。为了进一步确定这一缺陷的基础，对24名检测到MTX转运的白血病患者的白血病原始细胞的RNA进行了还原叶酸载体(RFC)的Northern分析。在9个MTX转运受损的样本中，6个样本的RFC表达降低(1个样本未检测到RFC表达)，3个白色样本的RFC表达没有下降。15例MTX转运正常的标本中无一例RFC表达降低。为了更准确地定量RFC基因的表达，建立了逆转录聚合酶链式反应(RT-PCR)方法。在9个MTX转运受损的样本中，有6个样本的RFC表达降低，这证实了Northern印迹的结果。这些数据表明，在接受含MTX治疗的复发性ALL患者中，观察到与MTX转运受损相关的RFC表达减少。(C)1997年由美国血液病学会主办。
Methotrexate (MTX) transport was examined in 27 patients with untreated acute lymphocytic leukemia (ALL) and 31 patients with relapsed ALL using a previously described fluorescent MTX analog (PT430) displacement assay (Blood 80:1158, 1992). Only 13% of untreated patients were considered to have impaired MTX transport, whereas more than 70% of relapsed patients had evidence of impaired MTX transport. To further characterize the basis for this defect, Northern analyses for the reduced folate carrier (RFC) were performed on the RNA available from the leukemic blasts of 24 patients in whom MTX transport had been measured. Six of nine samples with impaired MTX transport had decreased RFC expression (one had no detectable RFC expression), white three had no decrease in RFC expression. None of 15 samples with normal MTX transport had decreased RFC expression. A reverse-transcriptase polymerase chain reaction (RT-PCR) assay was developed to quantitate RFC mRNA expression more accurately. Decreased RFC expression was demonstrated in six of the nine samples with impaired MTX transport, confirming the results obtained by Northern blot. These data indicate decreased RFC expression associated with impaired MTX transport is observed in relapsed ALL following treatment with MTX-containing therapy. (C) 1997 by The American Society of Hematology.