Abstract
The Ph-negative chronic myeloproliferative disorders (CMPDs) polycythaemia vera, essential thrombocytosis and idiopathic myelofibrosis are acquired stem cell disorders, which pathophysiologically are featured by clonal myeloproliferation and accumulation of myeloid cells, the latter being consequent to decreased apoptosis. Myelofibrosis and neoangiogenesis in the bone marrow and spleen are the histopathological hallmarks of idiopathic myelofibrosis but may develop in the other diseases as well. In patients with myelofibrosis elevated levels of circulating CD34+ cells are highly characteristic being partly explained by a proteolytic bone marrow mileu owing to excessive release of various proteases with ensuing extracellular matrix degradation and constitutive mobilisation of CD34+ cells into the peripheral blood. Thrombohaemorrhagic complications are major clinical problems contributing significantly to morbidity and mortality. Based upon in vitro and in vivo studies of the effects of statins (antithrombotic, antiproliferative, antiangiogenic, antiproteolytic) and zoledronic acid (antiproliferative antiproliferative, antiangiogenic, antiproteolytic) this review focusses on the translation of these effects into potential clinical benefits of combinational therapy with these agents in patients with CMPDs.
Keywords: idiopathic myelofibrosis, Zoledronic acid, Farnesyl transferase inhibitors (FTI), Antiangiogenic, Proapoptotic
Current Drug Targets
Title: The Mevalonate Pathway as a Therapeutic Target in the Ph-Negative Chronic Myeloproliferative Disorders
Volume: 8 Issue: 2
Author(s): Hans Carl Hasselbalch and Caroline H. Riley
Affiliation:
Keywords: idiopathic myelofibrosis, Zoledronic acid, Farnesyl transferase inhibitors (FTI), Antiangiogenic, Proapoptotic
Abstract: The Ph-negative chronic myeloproliferative disorders (CMPDs) polycythaemia vera, essential thrombocytosis and idiopathic myelofibrosis are acquired stem cell disorders, which pathophysiologically are featured by clonal myeloproliferation and accumulation of myeloid cells, the latter being consequent to decreased apoptosis. Myelofibrosis and neoangiogenesis in the bone marrow and spleen are the histopathological hallmarks of idiopathic myelofibrosis but may develop in the other diseases as well. In patients with myelofibrosis elevated levels of circulating CD34+ cells are highly characteristic being partly explained by a proteolytic bone marrow mileu owing to excessive release of various proteases with ensuing extracellular matrix degradation and constitutive mobilisation of CD34+ cells into the peripheral blood. Thrombohaemorrhagic complications are major clinical problems contributing significantly to morbidity and mortality. Based upon in vitro and in vivo studies of the effects of statins (antithrombotic, antiproliferative, antiangiogenic, antiproteolytic) and zoledronic acid (antiproliferative antiproliferative, antiangiogenic, antiproteolytic) this review focusses on the translation of these effects into potential clinical benefits of combinational therapy with these agents in patients with CMPDs.
Export Options
About this article
Cite this article as:
Carl Hasselbalch Hans and Riley H. Caroline, The Mevalonate Pathway as a Therapeutic Target in the Ph-Negative Chronic Myeloproliferative Disorders, Current Drug Targets 2007; 8 (2) . https://dx.doi.org/10.2174/138945007779940133
DOI https://dx.doi.org/10.2174/138945007779940133 |
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
-
B7-H3-targeted Radioimmunotherapy of Human Cancer
Current Medicinal Chemistry Mechanism of Cancer Drug Resistance and the Involvement of Noncoding RNAs
Current Medicinal Chemistry Advances in Tumor Targeted Liposomes
Current Molecular Medicine A TRIBUTE TO A LIVING LEGEND (Special Issue in Honor of the 70th Birthday of Dr. Atta-ur-Rahman.)
Combinatorial Chemistry & High Throughput Screening Yeast as a Powerful Model System for the Study of Apoptosis Regulation by Protein Kinase C Isoforms
Current Pharmaceutical Design Antiproliferative Activity of Cobra Venom Cytotoxins
Current Topics in Medicinal Chemistry Targeted Therapy for Advanced Renal Cell Cancer: Cytokines and Beyond
Current Pharmaceutical Design Aminopeptidases of Malaria Parasites: New Targets for Chemotherapy
Infectious Disorders - Drug Targets Carotenoids as Modulators of Intracellular Signaling Pathways
Current Signal Transduction Therapy Interferon-Alpha in the Treatment of Philadelphia-Negative Chronic Myeloproliferative Neoplasms. Status and Perspectives
Current Drug Targets The Anticancer Properties of Dietary Polyphenols and its Relation with Apoptosis
Current Pharmaceutical Design Drug-Membrane Interactions: Significance for Medicinal Chemistry
Current Medicinal Chemistry Himalayan Plants as a Source of Anti-Cancer Agents: A Review
The Natural Products Journal Synthesis and Biological Evaluation of 2-, 3-, and 4-Acylaminocinnamyl-Nhydroxyamides as Novel Synthetic HDAC Inhibitors
Medicinal Chemistry Recent Patents Reveal Microtubules as Persistent Promising Target for Novel Drug Development for Cancers
Recent Patents on Anti-Infective Drug Discovery Cancer Stem Cells: The Emerging Challenge of Drug Targeting
Current Medicinal Chemistry Inhibition of Protein Kinase c-Src as a Therapeutic Approach for Cancer and Bone Metastases
Anti-Cancer Agents in Medicinal Chemistry The Molecular Bases of the Self-Renewal and Differentiation of Leukemic Stem Cells
Current Cancer Therapy Reviews Anticancer Drugs in Liposomal Nanodevices: A Target Delivery for a Targeted Therapy
Current Topics in Medicinal Chemistry Mesenchymal Cells in the Treatment of Spinal Cord Injury: Current & Future Perspectives
Current Stem Cell Research & Therapy