ABCA3 as a possible cause of drug resistance in childhood acute myeloid leukemia

Publication type:
Journal article
Metadata:
Autoren
  • Daniel Steinbach
  • Jean-Pierre Gillet
  • Axel Sauerbrey
  • Bernd Gruhn
  • Kristin Dawczynski
  • Vincent Bertholet
  • Francoise de Longueville
  • Felix Zintl
  • Jose Remacle
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000239373200031&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1158/1078-0432.CCR-05-2587
Externe Identifier
  • Clarivate Analytics Document Solution ID: 068KR
  • PubMed Identifier: 16857811
ISSN
1078-0432
Ausgabe der Veröffentlichung
14
Zeitschrift
CLINICAL CANCER RESEARCH
Paginierung
4357 - 4363
Datum der Veröffentlichung
2006
Status
Published
Titel
ABCA3 as a possible cause of drug resistance in childhood acute myeloid leukemia
Sub types
  • Article
Ausgabe der Zeitschrift
12

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:title>Abstract</jats:title> <jats:p>Background: A major issue in the treatment of acute myeloid leukemia (AML) is resistance to chemotherapeutic drugs. Multidrug resistance can be caused by ATP-binding cassette (ABC) transporters that function as drug efflux pumps. The majority of these proteins have not yet been examined in malignant diseases.</jats:p> <jats:p>Experimental Design: A newly developed microarray for the simultaneous quantification of 38 ABC transporter genes and Taqman real-time PCR was used to analyze the expression of ABC transporters in pediatric AML and healthy bone marrow. Small interfering RNA was used to verify the role of ABCA3 in drug resistance.</jats:p> <jats:p>Results: Using the microarray, we identified four new ABC transporters, which were overexpressed in many AML samples compared with healthy bone marrow: ABCA2, ABCA3, ABCB2, and ABCC10. The overexpression of these four genes was verified by real-time PCR in 42 samples from children with AML and 18 samples of healthy bone marrow. The median expression of ABCA3 was three times higher in 21 patients who had failed to achieve remission after the first course of chemotherapy than in a well-matched group of 21 patients who had achieved remission at this stage (P = 0.023). Incubation of cell lines with a number of different cytostatic drugs induced an up-regulation of ABCA3. Down-regulation of ABCA3 by small interfering RNA sensitized cells to doxorubicin.</jats:p> <jats:p>Conclusion: Our results show that ABCA2, ABCA3, ABCB2, and ABCC10 are overexpressed in childhood AML compared with healthy bone marrow. ABCA3 is the most likely transporter to cause drug resistance.</jats:p>
Autoren
  • Daniel Steinbach
  • Jean-Pierre Gillet
  • Axel Sauerbrey
  • Bernd Gruhn
  • Kristin Dawczynski
  • Vincent Bertholet
  • Françoise de Longueville
  • Felix Zintl
  • Jose Remacle
  • Thomas Efferth
DOI
10.1158/1078-0432.ccr-05-2587
eISSN
1557-3265
ISSN
1078-0432
Ausgabe der Veröffentlichung
14
Zeitschrift
Clinical Cancer Research
Sprache
en
Online publication date
2006
Paginierung
4357 - 4363
Datum der Veröffentlichung
2006
Status
Published
Herausgeber
American Association for Cancer Research (AACR)
Herausgeber URL
http://dx.doi.org/10.1158/1078-0432.ccr-05-2587
Datum der Datenerfassung
2022
Titel
ABCA3 as a Possible Cause of Drug Resistance in Childhood Acute Myeloid Leukemia
Ausgabe der Zeitschrift
12

Data source: Crossref

Abstract
<h4>Background</h4>A major issue in the treatment of acute myeloid leukemia (AML) is resistance to chemotherapeutic drugs. Multidrug resistance can be caused by ATP-binding cassette (ABC) transporters that function as drug efflux pumps. The majority of these proteins have not yet been examined in malignant diseases.<h4>Experimental design</h4>A newly developed microarray for the simultaneous quantification of 38 ABC transporter genes and Taqman real-time PCR was used to analyze the expression of ABC transporters in pediatric AML and healthy bone marrow. Small interfering RNA was used to verify the role of ABCA3 in drug resistance.<h4>Results</h4>Using the microarray, we identified four new ABC transporters, which were overexpressed in many AML samples compared with healthy bone marrow: ABCA2, ABCA3, ABCB2, and ABCC10. The overexpression of these four genes was verified by real-time PCR in 42 samples from children with AML and 18 samples of healthy bone marrow. The median expression of ABCA3 was three times higher in 21 patients who had failed to achieve remission after the first course of chemotherapy than in a well-matched group of 21 patients who had achieved remission at this stage (P = 0.023). Incubation of cell lines with a number of different cytostatic drugs induced an up-regulation of ABCA3. Down-regulation of ABCA3 by small interfering RNA sensitized cells to doxorubicin.<h4>Conclusion</h4>Our results show that ABCA2, ABCA3, ABCB2, and ABCC10 are overexpressed in childhood AML compared with healthy bone marrow. ABCA3 is the most likely transporter to cause drug resistance.
Addresses
  • Children's Hospital, University of Jena, Jena, Germany. Daniel@Steinba.ch
Autoren
  • Daniel Steinbach
  • Jean-Pierre Gillet
  • Axel Sauerbrey
  • Bernd Gruhn
  • Kristin Dawczynski
  • Vincent Bertholet
  • Françoise de Longueville
  • Felix Zintl
  • Jose Remacle
  • Thomas Efferth
  • Thomas Efferth
DOI
10.1158/1078-0432.ccr-05-2587
eISSN
1557-3265
Externe Identifier
  • PubMed Identifier: 16857811
Open access
false
ISSN
1078-0432
Ausgabe der Veröffentlichung
14 Pt 1
Zeitschrift
Clinical cancer research : an official journal of the American Association for Cancer Research
Schlüsselwörter
  • Bone Marrow Cells
  • Jurkat Cells
  • Humans
  • ATP-Binding Cassette Transporters
  • RNA, Small Interfering
  • Oligonucleotide Array Sequence Analysis
  • Cluster Analysis
  • Drug Resistance, Multiple
  • Gene Expression Regulation, Neoplastic
  • Drug Resistance, Neoplasm
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Male
  • Leukemia, Myeloid, Acute
Sprache
eng
Medium
Print
Paginierung
4357 - 4363
Datum der Veröffentlichung
2006
Status
Published
Datum der Datenerfassung
2006
Titel
ABCA3 as a possible cause of drug resistance in childhood acute myeloid leukemia.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
12

Data source: Europe PubMed Central

Abstract
BACKGROUND: A major issue in the treatment of acute myeloid leukemia (AML) is resistance to chemotherapeutic drugs. Multidrug resistance can be caused by ATP-binding cassette (ABC) transporters that function as drug efflux pumps. The majority of these proteins have not yet been examined in malignant diseases. EXPERIMENTAL DESIGN: A newly developed microarray for the simultaneous quantification of 38 ABC transporter genes and Taqman real-time PCR was used to analyze the expression of ABC transporters in pediatric AML and healthy bone marrow. Small interfering RNA was used to verify the role of ABCA3 in drug resistance. RESULTS: Using the microarray, we identified four new ABC transporters, which were overexpressed in many AML samples compared with healthy bone marrow: ABCA2, ABCA3, ABCB2, and ABCC10. The overexpression of these four genes was verified by real-time PCR in 42 samples from children with AML and 18 samples of healthy bone marrow. The median expression of ABCA3 was three times higher in 21 patients who had failed to achieve remission after the first course of chemotherapy than in a well-matched group of 21 patients who had achieved remission at this stage (P = 0.023). Incubation of cell lines with a number of different cytostatic drugs induced an up-regulation of ABCA3. Down-regulation of ABCA3 by small interfering RNA sensitized cells to doxorubicin. CONCLUSION: Our results show that ABCA2, ABCA3, ABCB2, and ABCC10 are overexpressed in childhood AML compared with healthy bone marrow. ABCA3 is the most likely transporter to cause drug resistance.
Autoren
  • Daniel Steinbach
  • Jean-Pierre Gillet
  • Axel Sauerbrey
  • Bernd Gruhn
  • Kristin Dawczynski
  • Vincent Bertholet
  • Françoise de Longueville
  • Felix Zintl
  • Jose Remacle
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/16857811
DOI
10.1158/1078-0432.CCR-05-2587
ISSN
1078-0432
Ausgabe der Veröffentlichung
14 Pt 1
Zeitschrift
Clin Cancer Res
Schlüsselwörter
  • ATP-Binding Cassette Transporters
  • Adolescent
  • Adult
  • Bone Marrow Cells
  • Child
  • Child, Preschool
  • Cluster Analysis
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Jurkat Cells
  • Leukemia, Myeloid, Acute
  • Male
  • Oligonucleotide Array Sequence Analysis
  • RNA, Small Interfering
Sprache
eng
Country
United States
Paginierung
4357 - 4363
PII
12/14/4357
Datum der Veröffentlichung
2006
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2007
Titel
ABCA3 as a possible cause of drug resistance in childhood acute myeloid leukemia.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
12

Data source: PubMed

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