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
-
New Challenges for ACE-Inhibitors in Vascular Diseases
Drug Design Reviews - Online (Discontinued) Recombinant Factor VIIA, its Clinical Properties, and the Tissue Factor Pathway of Coagulation
Mini-Reviews in Medicinal Chemistry VEGF Mediates ApoE4-Induced Neovascularization and Synaptic Pathology in the Choroid and Retina
Current Alzheimer Research Angiogenesis as Risk Factor for Plaque Vulnerability
Current Pharmaceutical Design The Endothelium and Platelets in Cardiovascular Disease: Potential Targets for Therapeutic Intervention
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Recent Patents on Biomedical Applications for the Treatment of Atherosclerosis
Recent Patents on Regenerative Medicine Editorial (Current and Emerging Pharmacological Therapies of Ischaemic Stroke)
CNS & Neurological Disorders - Drug Targets Vitamin E and All-Cause Mortality: A Meta-Analysis
Current Aging Science The Promise of Slow Down Ageing May Come from Curcumin
Current Pharmaceutical Design Impact of Drug Metabolism/Pharmacokinetics and their Relevance Upon Traditional Medicine-based Cardiovascular Drug Research
Current Drug Metabolism Role of Micronutrients on Subclinical Atherosclerosis Micronutrients in Subclinical Atherosclerosis
Current Pharmaceutical Design Inwardly Rectifying Potassium Channels in the Regulation of Vascular Tone
Current Drug Targets Editorial (Thematic Issue: Therapeutic Potential of microRNAs in Vascular Disease)
Current Vascular Pharmacology Arterial Accelerated Aging in Dialysis Patients: The Clinical Impact of Vascular Calcification
Current Vascular Pharmacology Old And New Oral Anticoagulants In Management Of Atrial Fibrillation: A Double-Edged Sword For Women
Current Vascular Pharmacology Structure and Expression of Different Serum Amyloid A (SAA) Variants and their Concentration-Dependent Functions During Host Insults
Current Medicinal Chemistry Cell and Gene Therapies in Cardiovascular Disease with Special Focus on the No Option Patient
Current Gene Therapy Psoriasis and Atherosclerosis: Is There a Need For Novel Biomarkers Assessing Cardiovascular Risk?
Current Pharmaceutical Design Ticagrelor: Long-Term Therapy in Patients with Coronary Artery Disease
Reviews on Recent Clinical Trials Serum Adiponectin Levels in Patients with Familial Mediterranean Fever
Protein & Peptide Letters