Abstract
The Ph-negative chronic myeloproliferative disorders (CMPDs) polycythaemia vera, essential thrombocytosis and idiopathic myelofibrosis are acquired stem cell disorders, which pathophysiologically are featured by clonal myeloproliferation and accumulation of myeloid cells, the latter being consequent to decreased apoptosis. Myelofibrosis and neoangiogenesis in the bone marrow and spleen are the histopathological hallmarks of idiopathic myelofibrosis but may develop in the other diseases as well. In patients with myelofibrosis elevated levels of circulating CD34+ cells are highly characteristic being partly explained by a proteolytic bone marrow mileu owing to excessive release of various proteases with ensuing extracellular matrix degradation and constitutive mobilisation of CD34+ cells into the peripheral blood. Thrombohaemorrhagic complications are major clinical problems contributing significantly to morbidity and mortality. Based upon in vitro and in vivo studies of the effects of statins (antithrombotic, antiproliferative, antiangiogenic, antiproteolytic) and zoledronic acid (antiproliferative antiproliferative, antiangiogenic, antiproteolytic) this review focusses on the translation of these effects into potential clinical benefits of combinational therapy with these agents in patients with CMPDs.
Keywords: idiopathic myelofibrosis, Zoledronic acid, Farnesyl transferase inhibitors (FTI), Antiangiogenic, Proapoptotic
Current Drug Targets
Title: The Mevalonate Pathway as a Therapeutic Target in the Ph-Negative Chronic Myeloproliferative Disorders
Volume: 8 Issue: 2
Author(s): Hans Carl Hasselbalch and Caroline H. Riley
Affiliation:
Keywords: idiopathic myelofibrosis, Zoledronic acid, Farnesyl transferase inhibitors (FTI), Antiangiogenic, Proapoptotic
Abstract: The Ph-negative chronic myeloproliferative disorders (CMPDs) polycythaemia vera, essential thrombocytosis and idiopathic myelofibrosis are acquired stem cell disorders, which pathophysiologically are featured by clonal myeloproliferation and accumulation of myeloid cells, the latter being consequent to decreased apoptosis. Myelofibrosis and neoangiogenesis in the bone marrow and spleen are the histopathological hallmarks of idiopathic myelofibrosis but may develop in the other diseases as well. In patients with myelofibrosis elevated levels of circulating CD34+ cells are highly characteristic being partly explained by a proteolytic bone marrow mileu owing to excessive release of various proteases with ensuing extracellular matrix degradation and constitutive mobilisation of CD34+ cells into the peripheral blood. Thrombohaemorrhagic complications are major clinical problems contributing significantly to morbidity and mortality. Based upon in vitro and in vivo studies of the effects of statins (antithrombotic, antiproliferative, antiangiogenic, antiproteolytic) and zoledronic acid (antiproliferative antiproliferative, antiangiogenic, antiproteolytic) this review focusses on the translation of these effects into potential clinical benefits of combinational therapy with these agents in patients with CMPDs.
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Cite this article as:
Carl Hasselbalch Hans and Riley H. Caroline, The Mevalonate Pathway as a Therapeutic Target in the Ph-Negative Chronic Myeloproliferative Disorders, Current Drug Targets 2007; 8 (2) . https://dx.doi.org/10.2174/138945007779940133
DOI https://dx.doi.org/10.2174/138945007779940133 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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