Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Retinoid resistance in leukemic cells

M Kizaki1, H Ueno, H Matsushita

  • 1Division of Hematology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.

Leukemia & Lymphoma
|May 1, 1997
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Gal4 Driver Transgenic Zebrafish: Powerful Tools to Study Developmental Biology, Organogenesis, and Neuroscience.

Advances in genetics·2016
Same author

Tol2-mediated transgenesis, gene trapping, enhancer trapping, and Gal4-UAS system.

Methods in cell biology·2016
Same author

Anti-factor IXa/X bispecific antibody (ACE910): hemostatic potency against ongoing bleeds in a hemophilia A model and the possibility of routine supplementation.

Journal of thrombosis and haemostasis : JTH·2014
Same author

Anti-factor IXa/X bispecific antibody (ACE910): hemostatic potency against ongoing bleeds in a hemophilia A model and the possibility of routine supplementation.

Journal of thrombosis and haemostasis : JTH·2014
Same author

Evaluation of the body fluid mode of automated hematology analyzer XN-series for extremely low peripheral white blood cell counts.

International journal of laboratory hematology·2013
Same author

Acute generalized exanthematous pustulosis during the puerperal period: a case report.

Clinical and experimental obstetrics & gynecology·2012

Acute promyelocytic leukemia (APL) patients often relapse due to all-trans retinoic acid (RA) resistance. Drug metabolism, including increased cytochrome P-450 and CRABP, appears to be a key factor in developing this resistance.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Acute promyelocytic leukemia (APL) shows high initial response rates to all-trans retinoic acid (RA).
  • However, acquired resistance to RA frequently develops in APL patients, leading to relapse despite initial treatment success.

Purpose of the Study:

  • To investigate the underlying mechanisms of acquired all-trans retinoic acid (RA) resistance in acute promyelocytic leukemia (APL) cells.
  • To explore potential molecular and pharmacological factors contributing to treatment failure.

Main Methods:

  • Analysis of retinoid receptor gene mutations in RA-resistant APL cell lines (UF-1).
  • Assessment of changes in all-trans RA metabolism, including plasma concentrations, and the role of enzymes like cytochrome P-450, CRABP, and P-glycoprotein.

Related Experiment Videos

Main Results:

  • No point mutations were found in the RAR-alpha gene's ligand-binding domain of RA-resistant UF-1 cells.
  • Continuous all-trans RA treatment led to reduced plasma RA concentrations.
  • Induction of cytochrome P-450, CRABP, and P-glycoprotein was observed, contributing to lower active retinoid levels.

Conclusions:

  • Acquired resistance to all-trans RA in APL is not solely due to mutations in the RAR-alpha gene.
  • Altered drug metabolism, including increased expression of metabolizing enzymes and transporters, plays a significant role in the development of RA resistance in APL.