The Potential Role of Proinflammatory Cytokines and Complement Components in the Development of Drug-Induced Neuropathy in Patients with Multiple Myeloma

Łuczkowska, Karolina; Rutka, Magdalena; Rogińska, Dorota; Paczkowska, Edyta; Baumert, Bartłomiej; Milczarek, Sławomir; Górska, Martyna; Kulig, Piotr; Osękowska, Bogumiła; Janowski, Michał; Safranow, Krzysztof; Sommerfeld, Krzysztof; Borowiecka, Ewa; Zawodny, Piotr; Koclęga, Anna; Helbig, Grzegorz

doi:10.3390/jcm10194584

Cited by 5 publications

(4 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It may re ect the body's anti-tumor effects. Our study found strong prognostic value for Complement 3 and IL-2R, but its role in myeloma remains unclear 44 .…”

Section: Discussionmentioning

confidence: 56%

A risk-scoring system for assessing prognosis in multiple myeloma patients based on a large real-world sample

Wang,

Yang,

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

Objective Multiple myeloma (MM) is an incurable malignancy with a diversity of clinical characteristics and prognoses. The commonly used staging system has obvious shortcomings. Exploring accurate prognostic models is essential. Methods A total of 1,276 newly diagnosed MM patients were selected from Zhongshan Hospital Fudan University between January 2010 and April 2021. After excluding patients with amyloidosis or other tumors, a total of 802 patients receiving standard first-line therapy were included. 703 patients in the non-transplant group (527 patients in the training set and 176 patients in the validation set) and 109 patients in the transplant group. We enrolled 41 baseline parameters including clinical, laboratory, and pathological features. We used univariate and multivariate Cox analyses to screen for factors associated with overall survival and to develop prognostic models. Results The final risk-scoring system includes ECOG score, extramedullary lesion, thrombocyte, reticulocyte, anion gap, hypercalcemia, complement C3, β2-microglobulin, cytogenetics and interleukin-2 receptor. We identify the optimal cut-off for the risk score and divide the patients into high-risk and low-risk groups. Kaplan-Meier curves and Log-rank tests showed that the risk score was significant with overall survival in the training set (P < 0.001), validation set (P < 0.001) and transplant group (P = 0.02). The time-dependent receiver operator characteristic curve shows that the risk score has a better predictive value than the commonly used staging system. Conclusion A novel MM risk score system is developed based on a large real-world sample. We have performed a comprehensive assessment of baseline disease characteristics, which is of high application and practice value.

show abstract

“…It may re ect the body's anti-tumor effects. Our study found strong prognostic value for Complement 3 and IL-2R, but its role in myeloma remains unclear 44 .…”

Section: Discussionmentioning

confidence: 56%

A risk-scoring system for assessing prognosis in multiple myeloma patients based on a large real-world sample

Wang,

Yang,

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Theories exist that involve amyloid deposits, the complement cascade, and cytokinemediated injury. 4 EDX studies confirm CIPN, identifying the nerve structures involved, the presence of axonal degeneration, and its severity. In the particular case of thalidomide, axonal damage compromises the amplitude of SNAPs, evidencing a decrease of 50% or more.…”

Section: Discussionmentioning

confidence: 85%

Thalidomide-induced sensory axonal polyneuropathy: A case report

Rodríguez¹,

Ortiz²,

Caleño³

et al. 2023

IPMRJ

View full text Add to dashboard Cite

Introduction: Several chemotherapeutic agents are currently available for the management of various malignancies; however, many are associated with adverse effects. A case of thalidomide- induced polyneuropathy is described below. Case Description: A 65year old man, with a history of secondary myelofibrosis in management with thalidomide, consulted for 5months of neuropathic pain and paresthesia in both hands. On physical examination, he presented hypoesthesia and hyperalgesia in both hands. In the electrodiagnostic studies (EDX) a sensory polyneuropathy of axonal type was concluded. Discussion: Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect that occurs in up to 70% of patients. Symptomatology includes motor and sensitive deficit. EDX studies confirm diagnoses and characteristics. For the particular case of thalidomide involvement is mainly axonal. There is no standard treatment for CIPN, but several drugs can improve symptoms. Conclusions: CIPN is a frequent complication in patients managed with chemotherapy. The physiatrist is the ideal professional to provide a comprehensive approach to this entity, in order to improve the patient’s functionality.

show abstract

“…The obtained results highlighted the importance of the role of proinflammatory cytokines. Moreover, we demonstrated the previously unknown effect of complement components on the development of BiPN [ 13 ]. In another study, we depicted that the exposure of PC12-derived nerve cells to BTZ leads to alterations in the miRNA expression in genes responsible for cell cycle, DNA repair, nerve processes and cell division.…”

Section: Introductionmentioning

confidence: 71%

Bortezomib-Induced Epigenetic Alterations in Nerve Cells: Focus on the Mechanisms Contributing to the Peripheral Neuropathy Development

Łuczkowska

Rogińska

Kulig

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

Bortezomib-induced peripheral neuropathy (BiPN) occurs in approximately 40% of patients with multiple myeloma. The induction of severe neuropathy entails the dose reduction or complete elimination of bortezomib (BTZ). Interestingly, discontinuation of BTZ mostly results in a reduction or complete resolution of peripheral neuropathy (PN) symptoms. Therefore, it is likely that the BiPN mechanisms are based on temporary/reversible changes such as epigenetic alterations. In this study, we examined the effect of treating nerve cells, differentiated from the Lund human mesencephalic (dLUHMES) cell line, with several low-dose BTZ (0.15 nM) applications. We showed a significant decrease in global histone H3 acetylation as well as histone H3 lysine 9 acetylation. Moreover, analysis of the genetic microarray showed changes mainly in epigenetic processes related to chromatin rearrangement, chromatin silencing, and gene silencing. GSEA analysis revealed three interesting signaling pathways (SIRT1, B-WICH and, b-Catenin) that may play a pivotal role in PN development. We also performed an analysis of the miRNA microarray which showed the interactions of miR-6810-5p with the genes MSN, FOXM1, TSPAN9, and SLC1A5, which are directly involved in neuroprotective processes, neuronal differentiation, and signal transduction. The study confirmed the existence of BTZ-induced complex epigenetic alterations in nerve cells. However, further studies are necessary to assess the reversibility of epigenetic changes and their potential impact on the induction/resolution of PN.

show abstract

The Potential Role of Proinflammatory Cytokines and Complement Components in the Development of Drug-Induced Neuropathy in Patients with Multiple Myeloma

Cited by 5 publications

References 50 publications

A risk-scoring system for assessing prognosis in multiple myeloma patients based on a large real-world sample

A risk-scoring system for assessing prognosis in multiple myeloma patients based on a large real-world sample

Thalidomide-induced sensory axonal polyneuropathy: A case report

Bortezomib-Induced Epigenetic Alterations in Nerve Cells: Focus on the Mechanisms Contributing to the Peripheral Neuropathy Development

Contact Info

Product

Resources

About