Abstract
Acute myeloid leukaemia (AML) comprises 80% of acute adult leukaemias and the disease has mostly an unfavourable outcome. Diagnostic criteria rely primarily on morphological classification, while prognostic evaluation is determined by cytogenetic methods. Survival is highly variable and it is a matter of debate, whether alternative therapeutic approaches may improve the effectiveness of conventional cytotoxic drug treatment. Two transmembrane proteins undoubtedly contribute to worse prognosis: Pglycoprotein (Pgp) and FLT3. Pgp is a transmembrane, ATP-cassette binding efflux pump that efficiently removes structurally unrelated xenobiotics from leukaemic blasts. This leads to inefficiency towards several cytotoxic drugs, hence the phenomenon is called multidrug resistance. FLT3 is a transmembrane tyrosine kinase and an internal tandem duplication can considerably augment its kinase activity. Both mechanisms lead to chemotherapy resistance and significantly shorter survival; thus several studies have been designed to treat patients via therapeutic measures that neutralize these proteins. This review focuses on the pathophysiological phenomena and the detection methods of Pgp and FLT3 as well as on novel therapeutic strategies that are offered by their inhibition.
Keywords: Acute myeloid leukaemia, P-Glycoprotein, FLT-3 Mutation
Current Medicinal Chemistry
Title: Pgp and FLT3: Identification and Modulation of Two Proteins that Lead to Chemotherapy Resistance in Acute Myeloid Leukemia
Volume: 14 Issue: 5
Author(s): Janos Kappelmayer, Miklos Udvardy and Peter Antal-Szalmas
Affiliation:
Keywords: Acute myeloid leukaemia, P-Glycoprotein, FLT-3 Mutation
Abstract: Acute myeloid leukaemia (AML) comprises 80% of acute adult leukaemias and the disease has mostly an unfavourable outcome. Diagnostic criteria rely primarily on morphological classification, while prognostic evaluation is determined by cytogenetic methods. Survival is highly variable and it is a matter of debate, whether alternative therapeutic approaches may improve the effectiveness of conventional cytotoxic drug treatment. Two transmembrane proteins undoubtedly contribute to worse prognosis: Pglycoprotein (Pgp) and FLT3. Pgp is a transmembrane, ATP-cassette binding efflux pump that efficiently removes structurally unrelated xenobiotics from leukaemic blasts. This leads to inefficiency towards several cytotoxic drugs, hence the phenomenon is called multidrug resistance. FLT3 is a transmembrane tyrosine kinase and an internal tandem duplication can considerably augment its kinase activity. Both mechanisms lead to chemotherapy resistance and significantly shorter survival; thus several studies have been designed to treat patients via therapeutic measures that neutralize these proteins. This review focuses on the pathophysiological phenomena and the detection methods of Pgp and FLT3 as well as on novel therapeutic strategies that are offered by their inhibition.
Export Options
About this article
Cite this article as:
Kappelmayer Janos, Udvardy Miklos and Antal-Szalmas Peter, Pgp and FLT3: Identification and Modulation of Two Proteins that Lead to Chemotherapy Resistance in Acute Myeloid Leukemia, Current Medicinal Chemistry 2007; 14 (5) . https://dx.doi.org/10.2174/092986707780059661
DOI https://dx.doi.org/10.2174/092986707780059661 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Clinical Trials of Targeted Alpha Therapy for Cancer
Reviews on Recent Clinical Trials Genetic Manipulation of Human Embryonic Stem Cells: A System to Study Early Human Development and Potential Therapeutic Applications
Current Gene Therapy The Role of Tregs in Cancer: Foxp3 as a Putative Target for Therapy
Current Signal Transduction Therapy Dibenzofurans from Lichens – A Pharmacological Overview
Current Topics in Medicinal Chemistry Natural Products Targeting Autophagy via the PI3K/Akt/mTOR Pathway as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Topoisomerase Enzymes as Therapeutic Targets for Cancer Chemotherapy
Medicinal Chemistry Cancer Stem Cells: The ‘Achilles Heel’ of Chemo-Resistant Tumors
Recent Patents on Anti-Cancer Drug Discovery Epigenetic Regulation and Therapeutic Approaches in Cancer
Current Topics in Medicinal Chemistry Poly(ADP-ribose)polymerase Inhibition - Where Now?
Current Medicinal Chemistry CXXC5 Associates with Smads to Mediate TNF-α Induced Apoptosis
Current Molecular Medicine Thromboembolic Complications in Malignant Haematological Disorders
Current Vascular Pharmacology Chronic Eosinophilic Leukemia, Not Otherwise Specified (CEL, NOS)
Current Cancer Therapy Reviews A Review of Natural and Synthetic Antioxidants Important for Health and Longevity
Current Medicinal Chemistry ANN-QSAR Model for Virtual Screening of Androstenedione C-Skeleton Containing Phytomolecules and Analogues for Cytotoxic Activity Against Human Breast Cancer Cell Line MCF-7
Combinatorial Chemistry & High Throughput Screening Polysaccharide Colloids as Smart Vehicles in Cancer Therapy
Current Pharmaceutical Design Potential Gene Therapy Strategies for Cancer Stem Cells
Current Gene Therapy MicroRNAs in Chronic Lymphocytic Leukemia: An Old Disease with New Genetic Insights
MicroRNA Recent Advance in the Research of Flavonoids as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Novel Therapeutic Strategies Against Cancer: Marine-derived Drugs May Be the Answer?
Anti-Cancer Agents in Medicinal Chemistry Ribonucleases, Nucleases and Antiangiogenins in Antiproliferative Activities
Current Signal Transduction Therapy