Tyrosine kinase inhibitor STI571 potentiates the pharmacologic activity of retinoic acid in acute promyelocytic leukemia cells: effects on the degradation of RARalpha and PML-RARalpha.

Blood
M Gianni'E Garattini

Abstract

The 2-phenylaminopyrimidine derivative STI571 is a selective inhibitor of c-Abl, c-kit, and platelet-derived growth factor-receptor tyrosine kinases and is presently in phase II-III clinical studies. Here, this study reports on a novel pharmacologic activity of the compound, ie, enhancement of the cyto-differentiating, growth-inhibitory, and apoptogenic actions of all-trans-retinoic acid (ATRA). Whereas STI571 is not a cytodifferentiating agent by itself, the compound interacts with ATRA and enhances the myeloid maturation program set in motion by the retinoid in the PML-RARalpha(+) acute promyelocytic leukemia NB4 and the PML-RARalpha(-) myeloblastic HL60 and U937 cell lines. In addition, STI571 relieves the cyto-differentiation block observed in the ATRA-resistant cell lines, NB4.R1, NB4.306, and NB4.007. In NB4 promyelocytes, a RARalpha agonist, but not an RXR agonist, can substitute for ATRA and interact with STI571. By contrast, STI571 is unique among c-Abl-specific tyrosine kinase inhibitors in modulating the pharmacologic activity of ATRA. In NB4 cells, enhanced cyto-differentiation results in increased up-regulation of the expression of a number of genes coding for myeloid differentiation markers, including CD11b, CD11c...Continue Reading

References

May 26, 1991·The New England Journal of Medicine·R P WarrellA Jakubowski
May 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·T R BreitmanS J Collins
Aug 30, 1994·Proceedings of the National Academy of Sciences of the United States of America·S RuchaudM Lanotte
Oct 28, 1994·Biochemical and Biophysical Research Communications·C Rochette-EglyM P Gaub
Jun 28, 1996·The Journal of Biological Chemistry·T GruneK J Davies
Jul 5, 1996·Biochemical and Biophysical Research Communications·M GiannìE Garattini
Jul 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C ChomienneL Degos
Nov 1, 1996·Anti-cancer Drugs·G Kaur, E A Sausville
Mar 28, 1998·Blood Cells, Molecules & Diseases·C Gambacorti-PasseriniN B Lydon
Jan 29, 1999·Journal of the National Cancer Institute·P le CoutreC Gambacorti-Passerini
Apr 14, 1999·Cell Death and Differentiation·P RodríguezJ Gómez-Márquez
Dec 22, 1999·The EMBO Journal·G BenoitM Lanotte
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·J ZhuH de Thé
Jan 5, 2000·The Journal of Clinical Investigation·B J Druker, N B Lydon
Aug 1, 1997·International Journal of Oncology·E GarattiniM Terao

❮ Previous
Next ❯

Citations

Nov 26, 2010·Frontiers of Medicine in China·Ying-Li WuGuo-Qiang Chen
Sep 8, 2011·Cell Biochemistry and Biophysics·Ren-Jie ZhouZhen-Zhou Yang
Jun 7, 2005·Biochemical and Biophysical Research Communications·Zhi-Hong XueQian Zhao
Mar 24, 2004·Leukemia Research·Geoffrey W Krystal
Dec 4, 2003·Pharmacology & Therapeutics·Asterios S TsiftsoglouIoannis S Vizirianakis
Nov 17, 2001·Current Opinion in Pharmacology·E Garattini, M Terao
Jan 5, 2002·Hematology/oncology Clinics of North America·C P Reynolds, R S Lemons
Feb 1, 2014·Cancer Treatment Reviews·Enrico GarattiniMineko Terao
Oct 3, 2018·Critical Reviews in Food Science and Nutrition·Xiaoling NiXun Cai
Jan 10, 2018·Oncotarget·Shenglong ZhuYong Q Chen
Nov 11, 2010·ACS Medicinal Chemistry Letters·Monica BinaschiEnrico Garattini

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.