Abstract
Background: Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal disorders of hematopoietic system, characterized by genetic, epigenetic or microenvironmental alterations of aging hematopoietic stem cells. Pathophysiology of MDS comprises the suppression of normal hematopoiesis and reduced myeloid progenitor cells differentiation, with the main consequence of peripheral cytopenias and increased risk to evolution in acute myeloid leukemia (AML).
Method: This review summarizes the evolving understanding of the role of genetic and epigenetic alterations involved in pathogenesis and current and future strategies for therapeutic targeting in myelodysplastic syndromes. Results: In addition to molecular characteristics, immune and microenvironmental factors in bone marrow of MDS patients may further modify the MDS manifestations, its clinical presentation, disease course, risk of transformation to AML and prognosis of MDS, as well as response to therapy. Current clinical response to therapy approaches are exerted both by epigenetic alterations and by induction of apoptosis. Conclusion: Future treatment strategies in preclinical and clinical investigations are directed towards new dosing schedules of existing drugs, new genetic and epigenetic targets and combination of different agents, including hypomethylation agents and histone deacetylase inhibitors.Keywords: Myelodysplastic syndromes, leukemia, mutations, epigenetic targets, pathogenesis, therapy, hypomethylating agents, microRNA.
Current Pharmaceutical Design
Title:Genetic and Epigenetic Drug Targets in Myelodysplastic Syndromes
Volume: 23 Issue: 1
Author(s): Karmen Stankov, Suncica Stankov and Jasmina Katanic
Affiliation:
Keywords: Myelodysplastic syndromes, leukemia, mutations, epigenetic targets, pathogenesis, therapy, hypomethylating agents, microRNA.
Abstract: Background: Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal disorders of hematopoietic system, characterized by genetic, epigenetic or microenvironmental alterations of aging hematopoietic stem cells. Pathophysiology of MDS comprises the suppression of normal hematopoiesis and reduced myeloid progenitor cells differentiation, with the main consequence of peripheral cytopenias and increased risk to evolution in acute myeloid leukemia (AML).
Method: This review summarizes the evolving understanding of the role of genetic and epigenetic alterations involved in pathogenesis and current and future strategies for therapeutic targeting in myelodysplastic syndromes. Results: In addition to molecular characteristics, immune and microenvironmental factors in bone marrow of MDS patients may further modify the MDS manifestations, its clinical presentation, disease course, risk of transformation to AML and prognosis of MDS, as well as response to therapy. Current clinical response to therapy approaches are exerted both by epigenetic alterations and by induction of apoptosis. Conclusion: Future treatment strategies in preclinical and clinical investigations are directed towards new dosing schedules of existing drugs, new genetic and epigenetic targets and combination of different agents, including hypomethylation agents and histone deacetylase inhibitors.Export Options
About this article
Cite this article as:
Stankov Karmen, Stankov Suncica and Katanic Jasmina, Genetic and Epigenetic Drug Targets in Myelodysplastic Syndromes, Current Pharmaceutical Design 2017; 23 (1) . https://dx.doi.org/10.2174/1381612822666161003160033
DOI https://dx.doi.org/10.2174/1381612822666161003160033 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Resveratrol as an Enhancer of Apoptosis in Cancer: A Mechanistic Review
Anti-Cancer Agents in Medicinal Chemistry The Role of miR-129-5p in Cancer: A Novel Therapeutic Target
Current Molecular Pharmacology The Roles of Endoplasmic Reticulum Stress in the Pathophysiological Development of Cartilage and Chondrocytes
Current Pharmaceutical Design Radiolabeled Imaging Probes Targeting Angiogenesis for Personalized Medicine
Current Pharmaceutical Design Snake Venom Phospholipases A2: A New Class of Antitumor Agents
Protein & Peptide Letters Glucocorticoid Receptor Antagonists
Current Topics in Medicinal Chemistry Metabolism and Structure-Function Relationships of Connective Tissue Glycosaminoglycans and Proteoglycans
Current Organic Chemistry Paeonol Inhibits Migration, Invasion and Bone Adhesion of Small Cell Lung Cancer Cells
Current Signal Transduction Therapy Potential Association Between TLR4 and Chitinase 3-Like 1 (CHI3L1/YKL-40) Signaling on Colonic Epithelial Cells in Inflammatory Bowel Disease and Colitis-Associated Cancer
Current Molecular Medicine The Chick Embryo Chorioallantoic Membrane as a Model for in vivo Research on Anti-Angiogenesis
Current Pharmaceutical Biotechnology Allelic Imbalances of the egfr Gene as Key Events in Breast Cancer Progression – the Concept of Committed Progenitor Cells
Current Cancer Drug Targets Flavonoids as Multi-Target Compounds in Drug Discovery
Mini-Reviews in Organic Chemistry Withdrawal Notice: Drug Repurposing for Prospective Anti-Cancer Agents Along with the Clinical Status of the Repurposed Drug
Anti-Cancer Agents in Medicinal Chemistry Nanoparticle-based Drug Delivery Systems for Targeted Epigenetics Cancer Therapy
Current Drug Targets microRNA in Chondrogenesis, Cartilage and Osteoarthritis
Current Rheumatology Reviews Association of GRP78, HIF-1α and BAG3 Expression with the Severity of Chronic Lymphocytic Leukemia
Anti-Cancer Agents in Medicinal Chemistry Cellular Signaling in Cartilage Tissue Engineering
Current Signal Transduction Therapy Berberine Exerts Anti-cancer Activity by Modulating Adenosine Monophosphate- Activated Protein Kinase (AMPK) and the Phosphatidylinositol 3-Kinase/ Protein Kinase B (PI3K/AKT) Signaling Pathways
Current Pharmaceutical Design VEGF/VEGFR Pathway Inhibitors as Anti-Angiogenic Agents: Present and Future
Current Cancer Drug Targets Sequence and Structural Elements in the Mechanism of Function of Rhodopsin-Like Family of G Protein-Coupled-Receptors
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery