THE ROLE OF NEUROTROPHINS AND ANGIOGENIC CYTOKINES IN THE PATHOPHYSIOLOGY OF PERIPHERAL NEUROPATHY IN PATIENTS WITH MULTIPLE MYELOMA
(Abstract release date: 05/18/17)
EHA Library. Łuczkowska K. 05/18/17; 182651; PB1937
Karolina Łuczkowska
Contributions
Contributions
Abstract
Abstract: PB1937
Type: Publication Only
Background
The introduction of new treatment modalities have changed significantly the prognosis of multiple myeloma (MM) patients. The novel drugs and schemes of treatment of MM have contributed to substantial extend of the overall survival time of patients. However, the administration of some of the treatments, e.g. thalidomide or bortezomib, is also associated with occurrence of a serious and common side-effect problem, which is the drug-induced peripheral neuropathy. The mechanism of the development of the peripheral neuropathy is poorly understood. Nevertheless, one of its potential cause, could be inadequate concentrations of crucial trophic factors, including neurotrophic and/or angiogenic factors, which are responsible for proliferation, differentiation, survival and death of neuronal and nonneuronal cells.
Aims
The aim of this study was to elucidate the potential relationship between concentration of neurotrophic and angiogenic factors and development of peripheral neuropathy in the natural clinical course of the disease and, especially, induced by treatment regimen: VMP (bortezomib, melphalan, prednisone) or VTD (bortezomib, thalidomide,dexamethason) in patients with MM.
Methods
Peripheral blood samples were collected from patients classified into two groups: i) patients with multiple myeloma, without neuropathy and before therapy; and ii) patients with peripheral neuropathy 3o or 4o induced in the course of VMP or VTD therapy. The control group consisted healthy aged matched subjects. Assessment of concentrations of neurotrophins (BDNF, NSE) and angiogenic factor (PDGF) were performed using Luminex technology, which utilize microbeads coated with fluorescently labeled antibodies.
Results
Concentration of BDNF, PDGF and NSE were significant decreased in patients after treatment regimen involving VMP or VTD who have developed peripheral neuropathy grade 3 or 4, compared with patients with newly diagnosed MM without neuropathy, before therapy and control healthy group. Additionally, plasma levels of both neurotrophins and PDGF in patients before therapy were higher, then in control group. Obtained results may be caused by the changes in an activity of the transcription factor NF-κB during the treatment of MM, since reduction of NF-kB concentration is associated with decrease in the transcription of genes encoding BDNF, NSE and PDGF.
Conclusion
Alterations in the concentration of BDNF, PDGF and NSE suggest the cause and effect relationship between these factors and the development of neuropathy in patients with MM. Comprehensive elucidation of this phenomenon may contribute to the extension of the knowledge concerning the pathogenesis of neuropathy, and might well lead to reduction of the incidence of polyneuropathy in MM patients in the future.
Session topic: 13. Myeloma and other monoclonal gammopathies - Biology
Keyword(s): Protein Expression, Multiple Myeloma
Abstract: PB1937
Type: Publication Only
Background
The introduction of new treatment modalities have changed significantly the prognosis of multiple myeloma (MM) patients. The novel drugs and schemes of treatment of MM have contributed to substantial extend of the overall survival time of patients. However, the administration of some of the treatments, e.g. thalidomide or bortezomib, is also associated with occurrence of a serious and common side-effect problem, which is the drug-induced peripheral neuropathy. The mechanism of the development of the peripheral neuropathy is poorly understood. Nevertheless, one of its potential cause, could be inadequate concentrations of crucial trophic factors, including neurotrophic and/or angiogenic factors, which are responsible for proliferation, differentiation, survival and death of neuronal and nonneuronal cells.
Aims
The aim of this study was to elucidate the potential relationship between concentration of neurotrophic and angiogenic factors and development of peripheral neuropathy in the natural clinical course of the disease and, especially, induced by treatment regimen: VMP (bortezomib, melphalan, prednisone) or VTD (bortezomib, thalidomide,dexamethason) in patients with MM.
Methods
Peripheral blood samples were collected from patients classified into two groups: i) patients with multiple myeloma, without neuropathy and before therapy; and ii) patients with peripheral neuropathy 3o or 4o induced in the course of VMP or VTD therapy. The control group consisted healthy aged matched subjects. Assessment of concentrations of neurotrophins (BDNF, NSE) and angiogenic factor (PDGF) were performed using Luminex technology, which utilize microbeads coated with fluorescently labeled antibodies.
Results
Concentration of BDNF, PDGF and NSE were significant decreased in patients after treatment regimen involving VMP or VTD who have developed peripheral neuropathy grade 3 or 4, compared with patients with newly diagnosed MM without neuropathy, before therapy and control healthy group. Additionally, plasma levels of both neurotrophins and PDGF in patients before therapy were higher, then in control group. Obtained results may be caused by the changes in an activity of the transcription factor NF-κB during the treatment of MM, since reduction of NF-kB concentration is associated with decrease in the transcription of genes encoding BDNF, NSE and PDGF.
Conclusion
Alterations in the concentration of BDNF, PDGF and NSE suggest the cause and effect relationship between these factors and the development of neuropathy in patients with MM. Comprehensive elucidation of this phenomenon may contribute to the extension of the knowledge concerning the pathogenesis of neuropathy, and might well lead to reduction of the incidence of polyneuropathy in MM patients in the future.
Session topic: 13. Myeloma and other monoclonal gammopathies - Biology
Keyword(s): Protein Expression, Multiple Myeloma
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