Analysis of Mesencephalic Astrocyte-derived Neurotrophic Factor in Multiple Myeloma
Amandine Dernoncourt1, Chloe Sauzay2, Jean Schmidt3
1Department of Internal Medicine and RECIF, Amiens-Picardie University Medical Center, Amiens, France; dernoncourt.amandine@chu-amiens.fr.
Background/Aim:
Multiple myeloma (MM) is characterized by high production of immunoglobulins resulting in a constant source of endoplasmic reticulum (ER)-stress. Mesencephalic astrocyte-derived neurotrophic factor (MANF) was identified as a possible circulating biomarker that could help in monitoring ER-stress mediated diseases.
Materials And Methods:
To assess the relevance of MANF in MM, we performed in silico and in vitro analysis in malignant cell lines including the myeloma cell line RPMI 8226. Serum MANF concentration was compared between healthy subjects (n=60), patients with MM (n=68), or those with monoclonal gammopathy of undetermined significance (MGUS) (n=73).
Results:
MANF mRNA expression was upregulated in the RPMI 8226 cell line, and higher secretion of MANF was measured in RPMI 8226 supernatant. Serum MANF levels were not significantly different between MM or MGUS patients and those in age- and sex-matched healthy controls.
Conclusion:
MANF was not validated as a biomarker of interest in MM patients. Its potential implication in myeloma pathogenesis should be investigated.
Insights
Mesencephalic astrocyte-derived neurotrophic factor (MANF) was investigated as a biomarker for multiple myeloma (MM) and endoplasmic reticulum (ER)-stress. MANF did not prove to be a reliable biomarker for MM patients in this study.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Multiple myeloma (MM) is characterized by excessive immunoglobulin production, leading to chronic endoplasmic reticulum (ER) stress.
- Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proposed as a potential circulating biomarker for ER-stress-related diseases.
Purpose of the Study:
- To evaluate the relevance of MANF as a biomarker in multiple myeloma (MM).
- To assess MANF's potential role in monitoring ER-stress associated with MM.
Main Methods:
- In silico and in vitro analyses were conducted on MM cell lines, including RPMI 8226.
- Serum MANF concentrations were compared between healthy individuals (n=60), MM patients (n=68), and monoclonal gammopathy of undetermined significance (MGUS) patients (n=73).
Main Results:
- MANF mRNA expression and secretion were upregulated in the RPMI 8226 myeloma cell line.
- Serum MANF levels showed no significant difference between MM or MGUS patients and age-/sex-matched healthy controls.
Conclusions:
- MANF was not validated as a significant biomarker for multiple myeloma (MM).
- Further investigation is warranted to explore MANF's potential role in the pathogenesis of myeloma.


