Analysis of single nucleotide polymorphism C3435T of the multidrug resistance gene MDR1 in acute lymphoblastic leukemia

Publication type:
Journal article
Metadata:
Autoren
  • T Efferth
  • A Sauerbrey
  • D Steinbach
  • E Gebhart
  • HG Drexler
  • H Miyachi
  • CR Chitambar
  • CM Becker
  • F Zintl
  • A Humeny
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000184195600030&DestLinkType=FullRecord&DestApp=WOS_CPL
eISSN
1791-2423
Externe Identifier
  • Clarivate Analytics Document Solution ID: 701YB
  • PubMed Identifier: 12851703
ISSN
1019-6439
Ausgabe der Veröffentlichung
2
Zeitschrift
INTERNATIONAL JOURNAL OF ONCOLOGY
Schlüsselwörter
  • doxorubicin
  • leukemia
  • MALDI-TOF-MS
  • multidrug resistance gene 1
  • P-glycoprotein
  • real time PCR
  • single nucleotide polymorphisms
Paginierung
509 - 517
Datum der Veröffentlichung
2003
Status
Published
Titel
Analysis of single nucleotide polymorphism C3435T of the multidrug resistance gene <i>MDR1</i> in acute lymphoblastic leukemia
Sub types
  • Article
Ausgabe der Zeitschrift
23

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
Multidrug resistance is an important mechanism responsible for refractoriness of leukemia and worse outcome of patients. Overexpression of the multidrug resistance gene, MDR1, is of prognostic relevance in acute myeloid leukemia, while its role in acute lymphoblastic leukemia (ALL) is still under debate. Single nucleotide polymorphisms (SNP) have been detected in the MDR1 gene. The C3435T polymorphism in this gene seems to have functional and clinical consequences. In the present investigation, we have analyzed the role of the C3435T SNP for drug resistance and prognosis of human ALL. The C3435T SNP was analyzed in 20 T-ALL cell lines and in blood samples from 53 ALL patients and 7 healthy donors. The cell line panel consisted of cell lines not prior exposed in vitro to cytostatic drugs as well as of drug-resistant lines which were selected in vitro by exposure to doxorubicin, vincristine, methotrexate, or hydroxyurea. We have developed a highly sensitive matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS)-based genotyping approach to survey the C3435T SNP. Furthermore, mRNA expression was determined by real time reverse-transcribed polymerase chain reaction and doxorubicin sensitivity by a growth inhibition assay. Surprisingly, we did not find a significant correlation between C3435T homo- or heterozygote genotypes and MDR1 mRNA expression of cell lines or blood samples from patients and healthy donors. Furthermore, there was no relationship between the response of the cell lines to doxorubicin and the C3435T genotypes. Homo- or heterozygosity did not correlate to survival of patients in the Kaplan-Meier analysis. In conclusion, we do not have reason to assume that the C3435T SNP contributes to drug resistance of ALL and prognosis of ALL patients.
Addresses
  • Virtual Campus Rhineland-Palatinate, D-55126 Mainz, Germany. thomas.efferth@web.de
Autoren
  • Thomas Efferth
  • Axel Sauerbrey
  • Daniel Steinbach
  • Erich Gebhart
  • Hans-Günther Drexler
  • Hayato Miyachi
  • Christopher R Chitambar
  • Cord-Michael Becker
  • Felix Zintl
  • Andreas Humeny
eISSN
1791-2423
Externe Identifier
  • PubMed Identifier: 12851703
Open access
false
ISSN
1019-6439
Ausgabe der Veröffentlichung
2
Zeitschrift
International journal of oncology
Schlüsselwörter
  • Tumor Cells, Cultured
  • Humans
  • Cyclophosphamide
  • Hydroxyurea
  • Vincristine
  • Methotrexate
  • Daunorubicin
  • Prednisone
  • Asparaginase
  • RNA, Messenger
  • Cytarabine
  • Antineoplastic Agents
  • Antineoplastic Combined Chemotherapy Protocols
  • Prognosis
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Case-Control Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Polymorphism, Single Nucleotide
  • Genes, MDR
  • Female
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Mercaptopurine
Sprache
eng
Medium
Print
Paginierung
509 - 517
Datum der Veröffentlichung
2003
Status
Published
Datum der Datenerfassung
2003
Titel
Analysis of single nucleotide polymorphism C3435T of the multidrug resistance gene MDR1 in acute lymphoblastic leukemia.
Sub types
  • Comparative Study
  • Journal Article
Ausgabe der Zeitschrift
23

Data source: Europe PubMed Central

Abstract
Multidrug resistance is an important mechanism responsible for refractoriness of leukemia and worse outcome of patients. Overexpression of the multidrug resistance gene, MDR1, is of prognostic relevance in acute myeloid leukemia, while its role in acute lymphoblastic leukemia (ALL) is still under debate. Single nucleotide polymorphisms (SNP) have been detected in the MDR1 gene. The C3435T polymorphism in this gene seems to have functional and clinical consequences. In the present investigation, we have analyzed the role of the C3435T SNP for drug resistance and prognosis of human ALL. The C3435T SNP was analyzed in 20 T-ALL cell lines and in blood samples from 53 ALL patients and 7 healthy donors. The cell line panel consisted of cell lines not prior exposed in vitro to cytostatic drugs as well as of drug-resistant lines which were selected in vitro by exposure to doxorubicin, vincristine, methotrexate, or hydroxyurea. We have developed a highly sensitive matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS)-based genotyping approach to survey the C3435T SNP. Furthermore, mRNA expression was determined by real time reverse-transcribed polymerase chain reaction and doxorubicin sensitivity by a growth inhibition assay. Surprisingly, we did not find a significant correlation between C3435T homo- or heterozygote genotypes and MDR1 mRNA expression of cell lines or blood samples from patients and healthy donors. Furthermore, there was no relationship between the response of the cell lines to doxorubicin and the C3435T genotypes. Homo- or heterozygosity did not correlate to survival of patients in the Kaplan-Meier analysis. In conclusion, we do not have reason to assume that the C3435T SNP contributes to drug resistance of ALL and prognosis of ALL patients.
Autoren
  • Thomas Efferth
  • Axel Sauerbrey
  • Daniel Steinbach
  • Erich Gebhart
  • Hans-Günther Drexler
  • Hayato Miyachi
  • Christopher R Chitambar
  • Cord-Michael Becker
  • Felix Zintl
  • Andreas Humeny
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/12851703
ISSN
1019-6439
Ausgabe der Veröffentlichung
2
Zeitschrift
Int J Oncol
Schlüsselwörter
  • Antineoplastic Agents
  • Antineoplastic Combined Chemotherapy Protocols
  • Asparaginase
  • Case-Control Studies
  • Cyclophosphamide
  • Cytarabine
  • Daunorubicin
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Female
  • Genes, MDR
  • Humans
  • Hydroxyurea
  • Male
  • Mercaptopurine
  • Methotrexate
  • Polymorphism, Single Nucleotide
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Prednisone
  • Prognosis
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tumor Cells, Cultured
  • Vincristine
Sprache
eng
Country
Greece
Paginierung
509 - 517
Datum der Veröffentlichung
2003
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2004
Titel
Analysis of single nucleotide polymorphism C3435T of the multidrug resistance gene MDR1 in acute lymphoblastic leukemia.
Sub types
  • Comparative Study
  • Journal Article
Ausgabe der Zeitschrift
23

Data source: PubMed

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