Defective transport is a common mechanism of acquired methotrexate resistance in acute lymphocytic leukemia and is associated with decreased reduced folate carrier expression Journal Article
| Authors: | Gorlick, R.; Goker, E.; Trippett, T.; Steinherz, P.; Elisseyeff, Y.; Mazumdar, M.; Flintoff, W. F.; Bertino, J. R. |
| Article Title: | Defective transport is a common mechanism of acquired methotrexate resistance in acute lymphocytic leukemia and is associated with decreased reduced folate carrier expression |
| Abstract: | 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), while 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. |
| Keywords: | adolescent; adult; child; aged; child, preschool; middle aged; carrier protein; human cell; major clinical study; cancer recurrence; methotrexate; reverse transcription polymerase chain reaction; gene expression; membrane proteins; drug resistance; drug uptake; carrier proteins; folic acid; acute lymphocytic leukemia; drug transport; membrane transport; biological transport; multidrug resistance; northern blotting; membrane transport proteins; blast crisis; leukemia, lymphocytic, acute; humans; human; priority journal; article; fluoresceins |
| Journal Title: | Blood |
| Volume: | 89 |
| Issue: | 3 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 1997-02-01 |
| Start Page: | 1013 |
| End Page: | 1018 |
| Language: | English |
| PUBMED: | 9028333 |
| PROVIDER: | scopus |
| DOI: | 10.1182/blood.V89.3.1013 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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