scholarly journals Dasatinib, high-dose imatinib and nilotinib for the treatment of imatinib-resistant chronic myeloid leukaemia: a systematic review and economic evaluation.

2012 ◽  
Vol 16 (23) ◽  
Author(s):  
E Loveman ◽  
K Cooper ◽  
J Bryant ◽  
JL Colquitt ◽  
GK Frampton ◽  
...  
Keyword(s):  
Systematic Review ◽  
Economic Evaluation ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
High Dose ◽  
Imatinib Resistant

scholarly journals Evaluating the endometabolic and bone health effects of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukaemia: a systematic review protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e030092
Author(s):  
Janatani Balakumaran ◽  
Tanisha Birk ◽  
Breanne Golemiec ◽  
Wryan Helmeczi ◽  
Jeyanth Inkaran ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Myeloid Leukaemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukaemia ◽  
Tyrosine Kinase Inhibitors ◽  
Health Effects ◽  
Bone Health ◽  
Kinase Inhibitors ◽  
Systematic Review Protocol ◽  
Review Protocol

IntroductionChronic Myeloid Leukaemia (CML) constitutes 15% of new adult leukaemia cases as well as 2%–3% of leukaemia in children under 15% and 9% of leukaemias in adolescents 15–19 years of age annually. The introduction of Tyrosine Kinase Inhibitors (TKI) therapy has dramatically improved survival in these patients, yet the off-target effects of this treatment may have long-term health impacts on CML survivors. The risk of adverse health outcomes is especially important in children, where TKI exposure may occur during critical windows of growth and puberty, and patients require treatment for prolonged periods of time. The aim of this systematic review protocol is to report on the methods used to conduct a systematic review to investigate the endometabolic and bone health effects of TKI therapy in CML.Methods and analysisSearches will be conducted in the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE from inception on August 1st, 2019. Searches may be updated while performing the systematic review to ensure new evidence is included if applicable. Grey literature search will include ClinicalTrials.gov and ProQuest Dissertations and Theses A&I. We will perform a meta-analysis if there are at least two studies reporting similar populations, interventions, methods and tracking the same outcome measures. The studies should also have similar age and sex distributions.Ethics and disseminationAs this is a systematic review protocol, it does not include patient data; therefore, Research Ethics Board approval is not indicated. The systematic review will be published in a peer-reviewed journal and presented at international conferences.PROSPERO registration numberCRD42018091175.

Carboxyamidotriazole inhibits cell growth of imatinib-resistant chronic myeloid leukaemia cells including T315I Bcr–Abl mutant by a redox-mediated mechanism

2011 ◽  
Vol 300 (2) ◽  
pp. 205-214 ◽  
Author(s):  
Chiara Corrado ◽  
Stefania Raimondo ◽  
Anna Maria Flugy ◽  
Simona Fontana ◽  
Alessandra Santoro ◽  
...  
Keyword(s):  
Cell Growth ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Imatinib Resistant

scholarly journals Cross-talk between Bcr-abl and the Thioredoxin System in Chronic Myeloid Leukaemia: Implications for CML Treatment

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 207
Author(s):  
Erin Clapper ◽  
Sicong Wang ◽  
Prahlad V. Raninga ◽  
Giovanna Di Trapani ◽  
Kathryn F. Tonissen
Keyword(s):  
Drug Resistance ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Therapeutic Potential ◽  
Cell Signalling ◽  
Thioredoxin Reductase ◽  
Mrna Levels ◽  
Protein Levels ◽  
Imatinib Resistant ◽  
Thioredoxin System

Chronic myeloid leukaemia (CML) is currently treated with inhibitors of the CML specific oncoprotein, bcr-abl. While this strategy is initially successful, drug resistance can become a problem. Therefore, new targets need to be identified to ensure the disease can be appropriately managed. The thioredoxin (Trx) system, comprised of Trx, thioredoxin reductase (TrxR), and NADPH, is an antioxidant system previously identified as a target for therapies aimed at overcoming drug resistance in other cancers. We assessed the effectiveness of TrxR inhibitors on drug resistant CML cells and examined links between TrxR and the bcr-abl cell-signalling pathway. Two TrxR inhibitors, auranofin and [Au(d2pype)2]Cl, increased intracellular ROS levels and elicited apoptosis in both sensitive and imatinib resistant CML cells. Inhibition of TrxR activity by these pharmacological inhibitors, or by specific siRNA, also resulted in decreased bcr-abl mRNA and protein levels, and lower bcr-abl downstream signalling activity, potentially enhancing the effectiveness of TrxR inhibitors as CML therapies. In addition, imatinib resistant CML cell lines showed upregulated expression of the Trx system. Furthermore, analysis of datasets showed that CML patients who did not respond to imatinib had higher Trx mRNA levels than patients who responded to treatment. Our study demonstrates a link between the Trx system and the bcr-abl protein and highlights the therapeutic potential of targeting the Trx system to improve CML patients’ outcomes.

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