Abstract
The molecular pathogenesis of the myeloproliferative disorders (MPD) is poorly understood, except for chronic myeloid leukemia (CML). Recently, several groups have discovered a novel recurrent unique acquired clonal mutation in a tyrosine-kinase JAK2 in patients with Philadelphia-negative MPD and other myeloid disorders. It consists in a guanineto- thymine change encoding a valine to phenylalanine at codon 617 (JAK2 V617F). JAK2 and the other members of the Janus kinase family are tyrosine kinases that function as intermediates between membrane receptors and intracellular signalling molecules. The mutation occurs within the enzymatically inactive JH2 pseudo-kinase domain that regulates the active JH1 kinase domain. The JAK2 activation leads to constitutive JAK and STAT (activators of transcription) hyperactivation with induction of growth factor hypersensitivity and cell transformation. Some authors have found a higher risk of vascular thrombosis and higher platelet activation when the mutation is present. Therefore, the JAK2 mutation offers a molecular target for new drugs investigation in a similar way to bcr/abl rearrangement in CML. For all these reasons, several studies related to JAK2 have arisen in the last year. In this report, we will review the literature and discuss its possible clinical and prognostic significance.
Keywords: Myeloproliferative diseases, JAK2
Cardiovascular & Hematological Agents in Medicinal Chemistry
Title: JAK2 as a Molecular Marker in Myeloproliferative Diseases
Volume: 5 Issue: 3
Author(s): R. Mata, D. Subira, A. Garcia-Raso and P. Llamas
Affiliation:
Keywords: Myeloproliferative diseases, JAK2
Abstract: The molecular pathogenesis of the myeloproliferative disorders (MPD) is poorly understood, except for chronic myeloid leukemia (CML). Recently, several groups have discovered a novel recurrent unique acquired clonal mutation in a tyrosine-kinase JAK2 in patients with Philadelphia-negative MPD and other myeloid disorders. It consists in a guanineto- thymine change encoding a valine to phenylalanine at codon 617 (JAK2 V617F). JAK2 and the other members of the Janus kinase family are tyrosine kinases that function as intermediates between membrane receptors and intracellular signalling molecules. The mutation occurs within the enzymatically inactive JH2 pseudo-kinase domain that regulates the active JH1 kinase domain. The JAK2 activation leads to constitutive JAK and STAT (activators of transcription) hyperactivation with induction of growth factor hypersensitivity and cell transformation. Some authors have found a higher risk of vascular thrombosis and higher platelet activation when the mutation is present. Therefore, the JAK2 mutation offers a molecular target for new drugs investigation in a similar way to bcr/abl rearrangement in CML. For all these reasons, several studies related to JAK2 have arisen in the last year. In this report, we will review the literature and discuss its possible clinical and prognostic significance.
Export Options
About this article
Cite this article as:
R. Mata , D. Subira , A. Garcia-Raso and P. Llamas , JAK2 as a Molecular Marker in Myeloproliferative Diseases, Cardiovascular & Hematological Agents in Medicinal Chemistry 2007; 5 (3) . https://dx.doi.org/10.2174/187152507781058654
DOI https://dx.doi.org/10.2174/187152507781058654 |
Print ISSN 1871-5257 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6182 |
Call for Papers in Thematic Issues
Medicinal Plants with Beneficial Properties on Diabetes and Hypertension
Diabetes and hypertension are real scourges of the 21st century. It is imperative to act in order to find innovative solutions to this problem. Taking medications such as hypoglycemic and antihypertensive drugs may aggravate certain underlying comorbidities, such as chronic kidney disease and cardiovascular disease. This significant drawback therefore requires ...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
-
Fibrinolytic Factors in Liver Fibrosis
Current Pharmaceutical Biotechnology Efficient Expression and Purification of Recombinant Therapeutic Protein Candidates, Human Midkine and Pleiotrophin
Current Pharmaceutical Biotechnology Intestinal MicrobiOMICS to Define Health and Disease in Human and Mice
Current Pharmaceutical Biotechnology Current Understanding of the Mechanism and Role of ROS in Angiotensin II Signal Transduction
Current Pharmaceutical Biotechnology Beneficial Effects of Statins on Endothelial Dysfunction and Vascular Stiffness
Current Vascular Pharmacology The Food-gut Human Axis: The Effects of Diet on Gut Microbiota and Metabolome
Current Medicinal Chemistry Vascular Disease and Risk Factors in Chronic Kidney Disease
Vascular Disease Prevention (Discontinued) Polydeoxyribonucleotide (PDRN): A Safe Approach to Induce Therapeutic Angiogenesis in Peripheral Artery Occlusive Disease and in Diabetic Foot Ulcers
Cardiovascular & Hematological Agents in Medicinal Chemistry Inflammasome as a New Therapeutic Target for Diabetic Complications
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Ethnopharmacological and Phytopharmaceutical Evaluation of Prosopis cineraria: An Overview and Future Prospects
Current Drug Metabolism Cardiovascular Remodeling Induced by Passive Smoking
Inflammation & Allergy - Drug Targets (Discontinued) Nongenomic Actions of Retinoids: Role of Nur77 and RXR in the Regulation of Apoptosis and Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Tangier Disease Four Decades of Research: A Reflection of the Importance of HDL
Current Medicinal Chemistry Neuroprotective Effects of Estrogens: Cross-Talk Between Estrogen and Intracellular Insulin Signalling
Infectious Disorders - Drug Targets A Coadunation of Biological and Mathematical Perspectives on the Pandemic COVID-19: A Review
Coronaviruses Genetic Variation in the β2-Adrenergic Receptor: Impact on Intermediate Cardiovascular Phenotypes
Current Pharmacogenomics and Personalized Medicine Are Cerebrovascular White Matter Lesions an Early Sign of Vascular Cognitive Impairment and Vascular Dementia?
Vascular Disease Prevention (Discontinued) Evaluation of Plasma Homocysteine Levels as a Prognostic Factor for the Occurrence of Perioperative Myocardial Infarction in Coronary Artery Bypass Grafting: A Pilot Study
Vascular Disease Prevention (Discontinued) Natural Products Triggering Biological Targets- A Review of the Anti-Inflammatory Phytochemicals Targeting the Arachidonic Acid Pathway in Allergy Asthma and Rheumatoid Arthritis
Current Drug Targets MicroRNAs-based Therapy: A Novel and Promising Strategy for Cancer Treatment
MicroRNA