Abstract
Malignant cell transformation is caused by mutations in distinct key regulatory genes involved in cell growth, apoptosis, senescence and differentiation. Particularly in human leukemia, chromosomal translocations involving crucial hematopoietic transcription factors are frequently causally linked to the disease. Transcription factors commonly have a modular structure, comprising distinct domains for DNA- binding, dimerization and protein-protein interaction. Each domain is functionally important and in principle accessible for a molecular-based therapeutic intervention. Uncovering the molecular structure of critical domains will allow the rational development of therapeutic agents that inhibit particular functions of leukemogenic transcription factors. However, so far most approaches are in the experimental stage. Among others, the RUNX1/ETO fusion protein, commonly found within acute myeloid leukemia cells carrying the translocation t(8;21), is currently intensively studied at the functional and structural level as well as in animal models. This combined effort has allowed the development of specific targeting approaches addressing different functional domains of the fusion protein. With a special focus on RUNX1/ETO we will discuss recent strategies to directly interfere with aberrant transcription factors to block their leukemogenic function.
Keywords: Transcription factor, targeting, RUNX1/ETO, protein-protein interaction, leukemia, chromosomal translocation
Current Drug Targets
Title: Molecular Targeting of Aberrant Transcription Factors in Leukemia: Strategies for RUNX1/ETO
Volume: 11 Issue: 9
Author(s): Christian Wichmann, Manuel Grez and Jorn Lausen
Affiliation:
Keywords: Transcription factor, targeting, RUNX1/ETO, protein-protein interaction, leukemia, chromosomal translocation
Abstract: Malignant cell transformation is caused by mutations in distinct key regulatory genes involved in cell growth, apoptosis, senescence and differentiation. Particularly in human leukemia, chromosomal translocations involving crucial hematopoietic transcription factors are frequently causally linked to the disease. Transcription factors commonly have a modular structure, comprising distinct domains for DNA- binding, dimerization and protein-protein interaction. Each domain is functionally important and in principle accessible for a molecular-based therapeutic intervention. Uncovering the molecular structure of critical domains will allow the rational development of therapeutic agents that inhibit particular functions of leukemogenic transcription factors. However, so far most approaches are in the experimental stage. Among others, the RUNX1/ETO fusion protein, commonly found within acute myeloid leukemia cells carrying the translocation t(8;21), is currently intensively studied at the functional and structural level as well as in animal models. This combined effort has allowed the development of specific targeting approaches addressing different functional domains of the fusion protein. With a special focus on RUNX1/ETO we will discuss recent strategies to directly interfere with aberrant transcription factors to block their leukemogenic function.
Export Options
About this article
Cite this article as:
Wichmann Christian, Grez Manuel and Lausen Jorn, Molecular Targeting of Aberrant Transcription Factors in Leukemia: Strategies for RUNX1/ETO, Current Drug Targets 2010; 11 (9) . https://dx.doi.org/10.2174/138945010792006744
DOI https://dx.doi.org/10.2174/138945010792006744 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
Related Articles
-
Pharmacokinetics-Pharmacology Disconnection of Herbal Medicines and its Potential Solutions with Cellular Pharmacokinetic-Pharmacodynamic Strategy
Current Drug Metabolism Leishmaniasis: Current Treatment and Prospects for New Drugs and Vaccines
Current Medicinal Chemistry Epigenetic Remodeling of Chromatin Architecture: Exploring Tumor Differentiation Therapies in Mesenchymal Stem Cells and Sarcomas
Current Stem Cell Research & Therapy Power from the Garden: Plant Compounds as Inhibitors of the Hallmarks of Cancer
Current Medicinal Chemistry Novel Monoclonal Antibodies for the Treatment of Chronic Lymphocytic Leukemia
Current Cancer Drug Targets Poly(ADP-ribose)polymerase Inhibition - Where Now?
Current Medicinal Chemistry PI3K/Akt/mTOR Pathway Inhibitors in Cancer: A Perspective on Clinical Progress
Current Medicinal Chemistry Cancer Pharmacogenomics: Germline DNA, Tumor DNA, or Both?
Current Pharmacogenomics White Poplar (Populus alba L.) Suspension Cultures as a Model System to Study Apoptosis Induced by Alfalfa Saponins
Anti-Cancer Agents in Medicinal Chemistry Update on the Principles and Novel Local and Systemic Therapies for the Treatment of Non-Infectious Uveitis
Inflammation & Allergy - Drug Targets (Discontinued) Targeting the p53-Family in Cancer and Chemosensitivity: Triple Threat
Current Drug Targets Dietary Phytochemicals in Chemoprevention of Cancer: An Update
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Wnt/beta-Catenin Signaling and Small Molecule Inhibitors
Current Pharmaceutical Design Promotion of Apoptosis in Cancer Cells by Selective Purine-Derived Pharmacological CDK Inhibitors: One Outcome, Many Mechanisms
Current Pharmaceutical Design Synthetic Src-Kinase Domain Inhibitors and Their Structural Requirements
Anti-Cancer Agents in Medicinal Chemistry Analysis of the Molecular Determinants of the Response of Chronic Myelogenous Leukaemia to Tyrosine Kinase Inhibitors
Current Pharmacogenomics Designing a Novel Multi-Epitope Vaccine Against Htlv-1 Related Adult T-cell Leukemia/Lymphoma: An In Silico Approach
Current Proteomics Malignant Mesothelioma: Biology, Diagnosis and Therapeutic Approaches
Current Molecular Pharmacology Epigenetic Interventions Increase the Radiation Sensitivity of Cancer Cells
Current Pharmaceutical Design Targeting Vesicle Trafficking: An Important Approach to Cancer Chemotherapy
Recent Patents on Anti-Cancer Drug Discovery