Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Medical Oncology
Published in: Medical Oncology 3/2011

01-09-2011 | Original Paper

Knockdown of SOD1 sensitizes the CD34+ CML cells to imatinib therapy

Authors: Li Liu, Renan Chen, Siyong Huang, Yanlan Wu, Guohui Li, Qiang Liu, Dandan Yin, Yingmin Liang

Published in: Medical Oncology | Issue 3/2011

Login to get access

Abstract

Leukemia stem cell is thought to be one of the leading causes of imatinib resistance and the resultant relapse of chronic myelogenous leukemia (CML). Eradicating the leukemia stem cells holds the promise of CML treatment. In this study, we found that the CD34+ subpopulation in the CML cell line K562 had a higher expression of SOD1 than that in the CD34 negative cells. Knockdown of SOD1 in CD34+ cells had no significant effects on cell survival and growth, while it sensitized the CD34+ cells to imatinib therapy. N-acetyl-L cysteine (NAC) blocked the pro-apoptotic effects of SOD1 knockdown, suggesting the antioxidant effects of SOD1 was essential for the resistance of CD34+ cells to imatinib therapy. In summary, our results suggest that antagonizing the enhanced endogenous antioxidant activity in leukemia stem cells sheds lights on CML therapy.
Literature
1.
Ben-Neriah Y, Daley GQ, Mes-Masson AM, Witte ON, Baltimore D. The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene. Science. 1986;233(4760):212–4.PubMedCrossRef
2.
Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2(5):561–6.PubMedCrossRef
3.
McGahon A, et al. BCR-ABL maintains resistance of chronic myelogenous leukemia cells to apoptotic cell death. Blood. 1994;83(5):1179–87.PubMed
4.
Deangelo DJ, Attar EC. Use of dasatinib and nilotinib in imatinib-resistant chronic myeloid leukemia: translating preclinical findings to clinical practice. Leuk Lymphoma. 2010;51(3):363–75.PubMedCrossRef
5.
Hughes TP, Branford S. Monitoring disease response to tyrosine kinase inhibitor therapy in CML. Hematol Am Soc Hematol Educ Prog. 2009:477–487.
6.
Breccia M, Alimena G. Nilotinib therapy in chronic myelogenous leukemia: the strength of high selectivity on BCR/ABL. Curr Drug Targets. 2009;10(6):530–6.PubMedCrossRef
7.
Weisberg E, Manley PW, Cowan-Jacob SW, Hochhaus A, Griffin JD. Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat Rev Cancer. 2007;7(5):345–56.PubMedCrossRef
8.
Gontarewicz A, et al. PHA-680626 exhibits anti-proliferative and pro-apoptotic activity on Imatinib-resistant chronic myeloid leukemia cell lines and primary CD34+ cells by inhibition of both Bcr-Abl tyrosine kinase and Aurora kinases. Leuk Res. 2008;32(12):1857–65.PubMedCrossRef
9.
Belloc F, et al. The stem cell factor-c-KIT pathway must be inhibited to enable apoptosis induced by BCR-ABL inhibitors in chronic myelogenous leukemia cells. Leukemia. 2009;23(4):679–85.PubMedCrossRef
10.
Konig H, et al. Enhanced BCR-ABL kinase inhibition does not result in increased inhibition of downstream signaling pathways or increased growth suppression in CML progenitors. Leukemia. 2008;22(4):748–55.PubMedCrossRef
11.
Tothova Z, et al. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell. 2007;128(2):325–39.PubMedCrossRef
12.
Naka K, et al. TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature. 2010;463(7281):676–80.PubMedCrossRef
13.
Ghaffari S. Oxidative stress in the regulation of normal and neoplastic hematopoiesis. Antioxid Redox Signal. 2008;10(11):1923–40.PubMedCrossRef
14.
Naka K, Muraguchi T, Hoshii T, Hirao A. Regulation of reactive oxygen species and genomic stability in hematopoietic stem cells. Antioxid Redox Signal. 2008;10(11):1883–94.PubMedCrossRef
15.
Bruns CK, Kopito RR. Impaired post-translational folding of familial ALS-linked Cu, Zn superoxide dismutase mutants. EMBO J. 2007;26(3):855–66.PubMedCrossRef
16.
Furukawa Y, O’Halloran TV. Posttranslational modifications in Cu, Zn-superoxide dismutase and mutations associated with amyotrophic lateral sclerosis. Antioxid Redox Signal. 2006;8(5–6):847–67.PubMedCrossRef
Metadata
Title
Knockdown of SOD1 sensitizes the CD34+ CML cells to imatinib therapy
Authors
Li Liu
Renan Chen
Siyong Huang
Yanlan Wu
Guohui Li
Qiang Liu
Dandan Yin
Yingmin Liang
Publication date
01-09-2011
Publisher
Springer US
Published in
Medical Oncology / Issue 3/2011
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9529-9

Other articles of this Issue 3/2011

Medical Oncology 3/2011 Go to the issue

Original Paper

Allogeneic haematopoietic stem cell transplantation as a salvage strategy for relapsed or refractory nasal NK/T-cell lymphoma

Original Paper

Bax expression remains unchanged following antisense treatment directed against BCL-2

Original Paper

Expression of CDK5/p35 in resected patients with non-small cell lung cancer: relation to prognosis

Original Paper

Chemotherapy in clear cell sarcoma

Original Paper

Comparison of PG-SGA, SGA and body-composition measurement in detecting malnutrition among newly diagnosed lung cancer patients in stage IIIB/IV and benign conditions

Original Paper

Clinical significance of Cox-2, Survivin and Bcl-2 expression in hepatocellular carcinoma (HCC)
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits