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
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
-
Therapeutic Proteins in Tumors and Targeted Therapeutic Agents for Cancer Patients
Protein & Peptide Letters Thalidomide Chemotherapy-Induced Peripheral Neuropathy: Actual Status and New Perspectives with Thalidomide Analogues Derivatives
Mini-Reviews in Medicinal Chemistry Latest Results for Anti-Angiogenic Drugs in Cancer Treatment
Current Pharmaceutical Design Established Human Cell Lines as Models to Study Anti-leukemic Effects of Flavonoids
Current Genomics Recombinant Immunotoxins for the Treatment of Chemoresistant Hematologic Malignancies
Current Pharmaceutical Design Defective Autophagy in Fibroblasts May Contribute to Fibrogenesis in Autoimmune Processes
Current Pharmaceutical Design Galectin-9 in Cancer Therapy
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Novel Subtype Specific and Universal Somatostatin Analogues: Clinical Potential and Pitfalls
Current Pharmaceutical Design Prostate-Apoptosis-Response-Gene-4: Biological Properties and their Potential Therapeutic Exploitation in Hematological Malignancies
Letters in Drug Design & Discovery Targeting MDM4 as a Novel Therapeutic Approach for Hematologic Malignancies
Current Cancer Drug Targets Status Quo in Antibody-Drug Conjugates - Can Glyco- Enzymes Solve the Current Challenges?
Protein & Peptide Letters Hematological Malignancies and Pregnancy. A Brief Review
Reviews on Recent Clinical Trials News in the Indications of Direct Oral Anticoagulants According to the American College of Chest Physicians 2016 Guidelines
Current Drug Metabolism How is Gene Transfection Able to Improve Current Chemotherapy? The Role of Combined Therapy in Cancer Treatment
Current Medicinal Chemistry Antifungal Therapy of Aspergillosis of the Central Nervous System and Aspergillus Endophthalmitis
Current Pharmaceutical Design Treatment for Cancer Patients with Oral Mucositis: Assessment Based on the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer in International Society of Oral Oncology (MASCC/ISOO) in 2013 and Proposal of Possible Novel Treatment with a Japanese Herbal Medicine
Current Pharmaceutical Design Molecular Monitoring of Immune Reconstitution After Haploidentical Stem Cell Transplantation
Current Stem Cell Research & Therapy Bortezomib and Arsenious Acid Synergistically Inhibit HL-60 Cells Viability in vitro and in vivo
Current Signal Transduction Therapy Combined Modality Treatment of Glioblastoma Multiforme: The Role of Temozolomide
Reviews on Recent Clinical Trials An update on the Management and Treatment of Deep Vein Thrombosis
Cardiovascular & Hematological Agents in Medicinal Chemistry