BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance

Blood
Mateusz KoptyraTomasz Skorski

Abstract

Mutations in the BCR/ABL kinase domain play a major role in resistance to imatinib mesylate (IM). We report here that BCR/ABL kinase stimulates reactive oxygen species (ROS), which causes oxidative DNA damage, resulting in mutations in the kinase domain. The majority of mutations involved A/T-->G/C and G/C-->A/T transitions, a phenotype detected previously in patients, which encoded clinically relevant amino acid substitutions, causing IM resistance. This effect was reduced in cells expressing BCR/ABL(Y177F) mutant, which does not elevate ROS. Inhibition of ROS in leukemia cells by the antioxidants pyrrolidine dithiocarbamate (PDTC), N-acetylcysteine (NAC), and vitamin E (VE) decreased the mutagenesis rate and frequency of IM resistance. Simultaneous administration of IM and an antioxidant exerted better antimutagenic effect than an antioxidant alone. Therefore, inhibition of ROS should diminish mutagenesis and enhance the effectiveness of IM.

References

Jan 1, 1992·Journal of Cancer Research and Clinical Oncology·K Aterman
Jan 1, 1973·Mutation Research·R L Capizzi, J W Jameson
Jan 1, 1995·Annals of Nutrition & Metabolism·V S GhalautG P Singh
Mar 1, 1997·Leukemia & Lymphoma·H GisslingerM Talpaz
Feb 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·V M FactorS S Thorgeirsson
Jun 2, 2000·The Journal of Biological Chemistry·M SattlerJ D Griffin
Nov 18, 2000·European Journal of Clinical Nutrition·S P BoyleA R Collins
Apr 11, 2001·Mutation Research·K J Claycombe, S N Meydani
Mar 15, 2002·Cell Biochemistry and Biophysics·A L LuD Y Chang
May 23, 2002·Biochimie·Christophe FleuryJean-Luc Vayssière
Jan 17, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Brian J Druker
Feb 8, 2003·The Lancet Oncology·Carlo B Gambacorti-PasseriniLeonardo Scapozza
Apr 4, 2003·Cancer Biology & Therapy·E Premkumar Reddy
May 8, 2003·The Journal of Biological Chemistry·Toshiro MatsudaThomas A Kunkel
May 21, 2003·Annals of Internal Medicine·Razelle KurzrockMoshe Talpaz
Jan 28, 2004·The Hematology Journal : the Official Journal of the European Haematology Association·Haifa-Kathrin Al-AliMichael Werner Nikolaus Deininger
Feb 26, 2004·Blood·Bruno Calabretta, Danilo Perrotti
Apr 28, 2004·Leukemia Research·Heiko van der KuipWalter E Aulitzky
Jun 15, 2004·Biochemical and Biophysical Research Communications·Masahide YamamotoOsamu Miura

❮ Previous
Next ❯

Citations

Jan 21, 2009·Apoptosis : an International Journal on Programmed Cell Death·Srabanti RakshitSantu Bandyopadhyay
Jun 12, 2012·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Yin XiaoLingbo Liu
May 1, 2007·Current Hematologic Malignancy Reports·Tomasz Skorski
Apr 1, 2008·Current Hematologic Malignancy Reports·Paul La Rosée, Andreas Hochhaus
Apr 29, 2010·Current Hematologic Malignancy Reports·G Vignir HelgasonTessa L Holyoake
Feb 14, 2012·Current Hematologic Malignancy Reports·Tomasz Skorski
Mar 20, 2012·Current Hematologic Malignancy Reports·N MuvarakF V Rassool
Feb 18, 2011·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Juan Luis Steegmann-Olmedillas
Oct 1, 2008·Indian Journal of Clinical Biochemistry : IJCB·Rizwan AhmadRaj K Singh
Jun 12, 2013·Mutation Research·David J AratenJames C Mulloy
Sep 24, 2010·Leukemia·I SlomaC J Eaves
Sep 17, 2010·Leukemia·D M RossJ V Melo
May 25, 2007·Nature Reviews. Cancer·Junia V Melo, David J Barnes
Jul 25, 2012·Nature Reviews. Cancer·Thomas O'HareMichael W Deininger
Feb 2, 2011·Nature Reviews. Clinical Oncology·Michael Deininger
May 15, 2007·Leukemia·T MughalJ M Goldman
Jan 19, 2011·The Journal of Biological Chemistry·Min HuangBeverly S Mitchell
Jan 10, 2009·The Journal of Biological Chemistry·Yin GaoJoya Chandra
Aug 19, 2008·Antioxidants & Redox Signaling·Saghi Ghaffari
Jun 6, 2009·Antioxidants & Redox Signaling·Georg T Wondrak
Aug 5, 2009·Antioxidants & Redox Signaling·Shazib PervaizSaghi Ghaffari
Aug 21, 2012·Antioxidants & Redox Signaling·Mary E IrwinJoya Chandra
May 2, 2007·Journal of the National Cancer Institute·Xiaoyan JiangConnie Eaves
May 2, 2007·Journal of the National Cancer Institute·Margret S Rodrigues, Martin Sattler
Dec 3, 2010·Cancer Research·Artur SlupianekTomasz Skorski
Apr 9, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tri NguyenSteven Grant
Jun 21, 2008·Acta Haematologica·John M Goldman, Junia V Melo
Aug 3, 2007·The Journal of Clinical Investigation·Daniel W Sherbenou, Brian J Druker

❮ 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.