Abstract
Myeloproliferative neoplasms (MPN) are debilitating stem cell-derived clonal myeloid malignancies. Conventional treatments for the BCR-ABL1-negative MPN including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) have, so far, been unsatisfactory. Following the discovery of dysregulated JAK-STAT signaling in patients with MPN, many efforts have been directed toward the development of molecularly targeted therapies, including inhibitors of JAK1 and JAK2. Ruxolitinib (previously known as INCB018424; Incyte Corporation, Wilmington, Delaware, USA) is a rationally designed potent oral JAK1 and JAK2 inhibitor that has undergone clinical trials in patients with PV, ET, and PMF. Ruxolitinib was approved on November 16, 2011 by the United States Food and Drug Administration for the treatment of intermediate or high-risk myelofibrosis (MF), including patients with PMF, post-PV MF, and post-ET MF. In randomized phase III studies, ruxolitinib treatment resulted in significant and durable reductions in splenomegaly and improvements in disease-related symptoms in patients with MF compared with placebo or best available therapy. The most common adverse events were anemia and thrombocytopenia, which were manageable and rarely led to discontinuation. This review addresses the cellular and molecular biology, and the clinical management of MPN.
Keywords: Essential thrombocythemia, janus kinase, JAK inhibitor, JAK-STAT, myelofibrosis, myeloproliferative neoplasms, polycythemia vera, primary myelofibrosis, quality of life, ruxolitinib, splenomegaly, symptoms.
Current Medicinal Chemistry
Title:Biology and Clinical Management of Myeloproliferative Neoplasms and Development of the JAK Inhibitor Ruxolitinib
Volume: 19 Issue: 26
Author(s): J. Mascarenhas, T. I. Mughal and S. Verstovsek
Affiliation:
Keywords: Essential thrombocythemia, janus kinase, JAK inhibitor, JAK-STAT, myelofibrosis, myeloproliferative neoplasms, polycythemia vera, primary myelofibrosis, quality of life, ruxolitinib, splenomegaly, symptoms.
Abstract: Myeloproliferative neoplasms (MPN) are debilitating stem cell-derived clonal myeloid malignancies. Conventional treatments for the BCR-ABL1-negative MPN including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) have, so far, been unsatisfactory. Following the discovery of dysregulated JAK-STAT signaling in patients with MPN, many efforts have been directed toward the development of molecularly targeted therapies, including inhibitors of JAK1 and JAK2. Ruxolitinib (previously known as INCB018424; Incyte Corporation, Wilmington, Delaware, USA) is a rationally designed potent oral JAK1 and JAK2 inhibitor that has undergone clinical trials in patients with PV, ET, and PMF. Ruxolitinib was approved on November 16, 2011 by the United States Food and Drug Administration for the treatment of intermediate or high-risk myelofibrosis (MF), including patients with PMF, post-PV MF, and post-ET MF. In randomized phase III studies, ruxolitinib treatment resulted in significant and durable reductions in splenomegaly and improvements in disease-related symptoms in patients with MF compared with placebo or best available therapy. The most common adverse events were anemia and thrombocytopenia, which were manageable and rarely led to discontinuation. This review addresses the cellular and molecular biology, and the clinical management of MPN.
Export Options
About this article
Cite this article as:
Mascarenhas J., I. Mughal T. and Verstovsek S., Biology and Clinical Management of Myeloproliferative Neoplasms and Development of the JAK Inhibitor Ruxolitinib, Current Medicinal Chemistry 2012; 19 (26) . https://dx.doi.org/10.2174/092986712803251511
DOI https://dx.doi.org/10.2174/092986712803251511 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Single Nucleotide Polymorphisms as the Efficient Prognostic Markers in Breast Cancer
Current Cancer Drug Targets Antiangiogenic Therapeutic Approaches in Multiple Myeloma
Current Cancer Drug Targets Survivin: Role in Normal Cells and in Pathological Conditions
Current Cancer Drug Targets Ex Vivo Liver – Directed Gene Therapy for the Treatment of Metabolic Diseases: Advances in Hepatocyte Transplantation and Retroviral Vectors
Current Gene Therapy Chemotherapy with Gemcitabine in Advanced Biliary Tract Carcinoma
Reviews on Recent Clinical Trials Amphotericin B: From Derivatives to Covalent Targeted Conjugates
Mini-Reviews in Medicinal Chemistry Immunotherapy of Human Cancers Using Gene Modified T Lymphocytes
Current Gene Therapy A Review of the Clinical, Radiological and Biochemical Characteristics and Genetic Causes of High Bone Mass Disorders
Current Drug Targets Diagnostics, Prognostic and Therapeutic Exploitation of Telomeres and Telomerase in Leukemias
Current Pharmaceutical Biotechnology The Tribbles-1 Protein in Humans: Roles and Functions in Health and Disease
Current Molecular Medicine Multiple Myeloma Bone Marrow Niche
Current Pharmaceutical Biotechnology Towards Cure of CML: Why We Need to Know More About CML Stem Cells?
Current Stem Cell Research & Therapy Targeting Rho GTPases by Peptidic Structures
Current Pharmaceutical Design CSPG4 in Cancer: Multiple Roles
Current Molecular Medicine The Role of Nicotinamide Phosphoribosyltransferase in Cerebral Ischemia
Current Topics in Medicinal Chemistry Chimeric Antigen Receptor T Cell Based Immunotherapy for Cancer
Current Stem Cell Research & Therapy Cancer Therapy-Induced Residual Bone Marrow Injury: Mechanisms of Induction and Implication for Therapy
Current Cancer Therapy Reviews Procarbazine – A Traditional Drug in the Treatment of Malignant Gliomas
Current Medicinal Chemistry The Need for Improvement of the Treatment of Advanced and Metastatic Cervical Cancer, the Rationale for Combined Chemo-Immunotherapy
Anti-Cancer Agents in Medicinal Chemistry Genetics of Bladder Malignant Tumors in Childhood
Current Genomics