Abstract
Nuclear inositide signalling is implicated in normal and pathological cell proliferation and differentiation in several distinct models. Among the key molecules of nuclear inositide pathways, phosphoinositide-phospholipase (PI-PLC) C β1 is essential for regulating hematopoiesis, particularly along myeloid and erythroid lineage. Moreover, Akt activation is associated with protein synthesis, via mTOR pathway, and with erythroid induction, through PI-PLCγ1 activation. Myelodysplastic syndromes (MDS) are a series of heterogeneous diseases characterized by ineffective hemopoiesis, with a variable risk of evolution into acute myeloid leukemia (AML). Therapeutic approaches for MDS include demethylating agents, such as azacitidine, aiming at reducing cell proliferation, and erythropoietin, useful for sustaining a normal erythropoiesis. In the last few years, a role for nuclear inositide signalling as a therapeutic target in MDS has been disclosed, in that PI-PLCβ1 increase is associated with azacitidine responsiveness, even when this drug is used in combination with other agents, and Akt is specifically activated in MDS at higher risk of AML evolution. On the other hand, recent data demonstrated that inositide signalling can also be involved in erythroid therapy, given the inhibitory effect of erythropoietin on PI-PLCβ1 and the activation of Akt/PI-PLCγ1 pathway, following the administration of erythropoietin. Here, we review the strategic role of nuclear inositide signalling in MDS, in pathogenesis and therapy.
Keywords: Akt, azacitidine, erythropoietin, erythroid differentiation, myelodysplastic syndromes, myeloid differentiation, nuclear inositides, phospholipase Cβ1.
Mini-Reviews in Medicinal Chemistry
Title:Strategic Role of Nuclear Inositide Signalling in Myelodysplastic Syndromes Therapy
Volume: 14 Issue: 11
Author(s): Lucia Manzoli, Sara Mongiorgi, Cristina Clissa, Carlo Finelli, Anna Maria Billi, Alessandro Poli, Marilisa Quaranta, Lucio Cocco and Matilde Y. Follo
Affiliation:
Keywords: Akt, azacitidine, erythropoietin, erythroid differentiation, myelodysplastic syndromes, myeloid differentiation, nuclear inositides, phospholipase Cβ1.
Abstract: Nuclear inositide signalling is implicated in normal and pathological cell proliferation and differentiation in several distinct models. Among the key molecules of nuclear inositide pathways, phosphoinositide-phospholipase (PI-PLC) C β1 is essential for regulating hematopoiesis, particularly along myeloid and erythroid lineage. Moreover, Akt activation is associated with protein synthesis, via mTOR pathway, and with erythroid induction, through PI-PLCγ1 activation. Myelodysplastic syndromes (MDS) are a series of heterogeneous diseases characterized by ineffective hemopoiesis, with a variable risk of evolution into acute myeloid leukemia (AML). Therapeutic approaches for MDS include demethylating agents, such as azacitidine, aiming at reducing cell proliferation, and erythropoietin, useful for sustaining a normal erythropoiesis. In the last few years, a role for nuclear inositide signalling as a therapeutic target in MDS has been disclosed, in that PI-PLCβ1 increase is associated with azacitidine responsiveness, even when this drug is used in combination with other agents, and Akt is specifically activated in MDS at higher risk of AML evolution. On the other hand, recent data demonstrated that inositide signalling can also be involved in erythroid therapy, given the inhibitory effect of erythropoietin on PI-PLCβ1 and the activation of Akt/PI-PLCγ1 pathway, following the administration of erythropoietin. Here, we review the strategic role of nuclear inositide signalling in MDS, in pathogenesis and therapy.
Export Options
About this article
Cite this article as:
Manzoli Lucia, Mongiorgi Sara, Clissa Cristina, Finelli Carlo, Billi Maria Anna, Poli Alessandro, Quaranta Marilisa, Cocco Lucio and Follo Y. Matilde, Strategic Role of Nuclear Inositide Signalling in Myelodysplastic Syndromes Therapy, Mini-Reviews in Medicinal Chemistry 2014; 14 (11) . https://dx.doi.org/10.2174/1389557514666141013125936
DOI https://dx.doi.org/10.2174/1389557514666141013125936 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...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
-
The Role of miRNAs in Plasma Cell Dyscrasias
MicroRNA Preclinical and Clinical Studies of Chidamide (CS055/HBI-8000), An Orally Available Subtype-selective HDAC Inhibitor for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry The Use of Technetium-99m Radiolabeled Human Antimicrobial Peptides for Infection Specific Imaging
Mini-Reviews in Medicinal Chemistry Radioimmunotherapy of Solid Tumors: Searching for the Right Target
Current Drug Delivery Lymphoproliferative Disorders and Chemokines
Current Drug Targets Current Status and Future of Antifungal Therapy for Systemic Mycoses
Recent Patents on Anti-Infective Drug Discovery Pharmacodynamics and Pharmacokinetics of Antifungals for Treatment of Invasive Aspergillosis
Current Pharmaceutical Design Vascular Endothelial Growth Factor Receptors [VEGFR] as Target in Breast Cancer Treatment: Current Status in Preclinical and Clinical Studies and Future Directions
Current Topics in Medicinal Chemistry Physiology of Immune System: Regulation of Stem Cell Survival
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery The Influence of Macrophages and the Tumor Microenvironment on Natural Killer Cells
Current Molecular Medicine Flavonoids Acting on DNA Topoisomerases: Recent Advances and Future Perspectives in Cancer Therapy
Current Medicinal Chemistry Molecular Chaperone Hsp90 as a Target for Oxidant-Based Anticancer Therapies
Current Medicinal Chemistry Cellular Senescence and Anti-Cancer Therapy
Current Drug Targets Rheumatic Manifestations in Malignancy
Current Rheumatology Reviews Teratogenic Activity of HDAC Inhibitors
Current Pharmaceutical Design Acute Myeloid Leukemia in the Elderly: Current Therapeutic Results and Perspectives for Clinical Research
Reviews on Recent Clinical Trials Biologics for the Treatment of Juvenile Idiopathic Arthritis
Current Medicinal Chemistry TRAIL as Biomarker and Potential Therapeutic Tool for Cardiovascular Diseases
Current Drug Targets Stromal Cell Derived Factor-1 / CXCL12, CXCR4 and CD26 in the Mobilization and Homing of Hematopoietic Stem and Progenitor Cells
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Natural Products as Exquisitely Potent Cytotoxic Payloads for Antibody- Drug Conjugates
Current Topics in Medicinal Chemistry