Contribution of multiple myeloma-derived exosomes to bone disease

Our case demonstrates severe bone disease in primary AL-amyloidosis without concomitant multiple myeloma. A 30-year-old man had spontaneous vertebral fracture Th8. A computed tomography scan suggested multiple foci of lesions in all the bones. In bone marrow and resected rib werent detected any tumor cells. After 15 years from the beginning of the disease, nephrotic syndrome developed. Based on the kidney biopsy, AL-amyloidosis was confirmed. Amyloid was also detected in the bowel and bone marrow. On the indirect signs (thickening of the interventricular septum 16 mm and increased NT-proBNP 2200 pg/ml), a cardial involvement was confirmed. In the bone marrow (from three sites) was found 2.85% clonal plasma cells with immunophenotype СD138+, СD38dim, СD19-, СD117+, СD81-, СD27-, СD56-. FISH method revealed polysomy 5,9,15 in 3% of the nuclei. Serum free light chain Kappa 575 mg/l (/44.9) was detected. Multiple foci of destruction with increased metabolic activity (SUVmax 3.6) were visualized on PET-CT, and an surgical intervention biopsy was performed from two foci. The number of plasma cells from the destruction foci was 2.5%, and massive amyloid deposition was detected. On CT scan foci of lesions differed from bone lesions at multiple myeloma. Bone fragments of point and linear type (button sequestration) were visualized in most of the destruction foci. The content of the lesion was low density. There was no extraossal spread from large zones of destruction. There was also spontaneous scarring of the some lesions (without therapy). Thus, the diagnosis of multiple myeloma was excluded on the basis based on x-ray signs, of the duration of osteodestructive syndrome (15 years), the absence of plasma infiltration in the bone marrow, including from foci of bone destruction by open biopsy. This observation proves the possibility of damage to the skeleton due to amyloid deposition and justifies the need to include AL-amyloidosis in the spectrum of differential diagnosis of diseases that occur with osteodestructive syndrome.

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Impact of Natural Dietary Agents on Multiple Myeloma Prevention and Treatment: Molecular Insights and Potential for Clinical Translation

Current Medicinal Chemistry ◽

10.2174/0929867325666180629153141 ◽

2020 ◽

Vol 27 (2) ◽

pp. 187-215 ◽

Cited By ~ 8

Author(s):

Lavinia Raimondi ◽

Angela De Luca ◽

Gianluca Giavaresi ◽

Agnese Barone ◽

Pierosandro Tagliaferri ◽

...

Keyword(s):

Signal Transduction ◽

Multiple Myeloma ◽

Natural Products ◽

Bone Disease ◽

Molecular Mechanisms ◽

Plasma Cells ◽

Hematologic Malignancy ◽

Signal Transduction Pathways ◽

Pharmacologically Active ◽

Dietary Agents

: Chemoprevention is based on the use of non-toxic, pharmacologically active agents to prevent tumor progression. In this regard, natural dietary agents have been described by the most recent literature as promising tools for controlling onset and progression of malignancies. Extensive research has been so far performed to shed light on the effects of natural products on tumor growth and survival, disclosing the most relevant signal transduction pathways targeted by such compounds. Overall, anti-inflammatory, anti-oxidant and cytotoxic effects of dietary agents on tumor cells are supported either by results from epidemiological or animal studies and even by clinical trials. : Multiple myeloma is a hematologic malignancy characterized by abnormal proliferation of bone marrow plasma cells and subsequent hypercalcemia, renal dysfunction, anemia, or bone disease, which remains incurable despite novel emerging therapeutic strategies. Notably, increasing evidence supports the capability of dietary natural compounds to antagonize multiple myeloma growth in preclinical models of the disease, underscoring their potential as candidate anti-cancer agents. : In this review, we aim at summarizing findings on the anti-tumor activity of dietary natural products, focusing on their molecular mechanisms, which include inhibition of oncogenic signal transduction pathways and/or epigenetic modulating effects, along with their potential clinical applications against multiple myeloma and its related bone disease.

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Serum levels of macrophage inflammatory protein-1 alpha (MIP-1α) correlate with the extent of bone disease and survival in patients with multiple myeloma

British Journal of Haematology ◽

10.1046/j.1365-2141.2003.04561.x ◽

2003 ◽

Vol 123 (1) ◽

pp. 106-109 ◽

Cited By ~ 114

Author(s):

Evangelos Terpos ◽

Marianna Politou ◽

Richard Szydlo ◽

John M. Goldman ◽

Jane F. Apperley ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Disease ◽

Serum Levels ◽

Inflammatory Protein ◽

Macrophage Inflammatory Protein

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A Molecular Signature of Circulating MicroRNA Can Predict Osteolytic Bone Disease in Multiple Myeloma

Cancers ◽

10.3390/cancers13153877 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3877

Author(s):

Aristea-Maria Papanota ◽

Panagiotis Tsiakanikas ◽

Christos K. Kontos ◽

Panagiotis Malandrakis ◽

Christine-Ivy Liacos ◽

...

Keyword(s):

Multiple Myeloma ◽

Logistic Regression ◽

Bone Disease ◽

Characteristic Curve ◽

Molecular Signature ◽

Circulating Microrna ◽

Prognostic Role ◽

Clinical Value ◽

Osteolytic Bone Disease ◽

Circulating Levels

Background: Multiple myeloma bone disease (MMBD) constitutes a common and severe complication of multiple myeloma (MM), impacting the quality of life and survival. We evaluated the clinical value of a panel of 19 miRNAs associated with osteoporosis in MMBD. Methods: miRNAs were isolated from the plasma of 62 newly diagnosed MM patients with or without MMBD. First-strand cDNA was synthesized, and relative quantification was performed using qPCR. Lastly, we carried out extensive biostatistical analysis. Results: Circulating levels of let-7b-5p, miR-143-3p, miR-17-5p, miR-214-3p, and miR-335-5p were significantly higher in the blood plasma of MM patients with MMBD compared to those without. Receiver operating characteristic curve and logistic regression analyses showed that these miRNAs could accurately predict MMBD. Furthermore, a standalone multi-miRNA–based logistic regression model exhibited the best predictive potential regarding MMBD. Two of those miRNAs also have a prognostic role in MM since survival analysis indicated that lower circulating levels of both let-7b-5p and miR-335-5p were associated with significantly worse progression-free survival, independently of the established prognostic factors. Conclusions: Our study proposes a miRNA signature to facilitate MMBD diagnosis, especially in ambiguous cases. Moreover, we provide evidence of the prognostic role of let-7b-5p and miR-335-5p as non-invasive prognostic biomarkers in MM.

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Diagnosis and Treatment of Bone Disease in Multiple Myeloma: Spotlight on Spinal Involvement

Scientifica ◽

10.1155/2013/104546 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 14

Author(s):

Patrizia Tosi

Keyword(s):

Spinal Cord ◽

Multiple Myeloma ◽

Bone Marrow ◽

Bone Resorption ◽

Spinal Cord Compression ◽

Bone Disease ◽

Cord Compression ◽

Diagnosis And Treatment ◽

Conventional Chemotherapy ◽

Spinal Involvement

Bone disease is observed in almost 80% of newly diagnosed symptomatic multiple myeloma patients, and spine is the bone site that is more frequently affected by myeloma-induced osteoporosis, osteolyses, or compression fractures. In almost 20% of the cases, spinal cord compression may occur; diagnosis and treatment must be carried out rapidly in order to avoid a permanent sensitive or motor defect. Although whole body skeletal X-ray is considered mandatory for multiple myeloma staging, magnetic resonance imaging is presently considered the most appropriate diagnostic technique for the evaluation of vertebral alterations, as it allows to detect not only the exact morphology of the lesions, but also the pattern of bone marrow infiltration by the disease. Multiple treatment modalities can be used to manage multiple myeloma-related vertebral lesions. Surgery or radiotherapy is mainly employed in case of spinal cord compression, impending fractures, or intractable pain. Percutaneous vertebroplasty or balloon kyphoplasty can reduce local pain in a significant fraction of treated patients, without interfering with subsequent therapeutic programs. Systemic antimyeloma therapy with conventional chemotherapy or, more appropriately, with combinations of conventional chemotherapy and compounds acting on both neoplastic plasma cells and bone marrow microenvironment must be soon initiated in order to reduce bone resorption and, possibly, promote bone formation. Bisphosphonates should also be used in combination with antimyeloma therapy as they reduce bone resorption and prolong patients survival. A multidisciplinary approach is thus needed in order to properly manage spinal involvement in multiple myeloma.

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Comparison of the diagnostic performance and impact on management of 18F-FDG PET/CT and whole-body MRI in multiple myeloma

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05182-2 ◽

2021 ◽

Author(s):

Olwen Westerland ◽

◽

Ashik Amlani ◽

Christian Kelly-Morland ◽

Michal Fraczek ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Data ◽

Bone Disease ◽

Fdg Pet ◽

Diagnostic Performance ◽

Whole Body ◽

Bone Lesions ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

Abstract Purpose Comparative data on the impact of imaging on management is lacking for multiple myeloma. This study compared the diagnostic performance and impact on management of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and whole-body magnetic resonance imaging (WBMRI) in treatment-naive myeloma. Methods Forty-six patients undergoing 18F-FDG PET/CT and WBMRI were reviewed by a nuclear medicine physician and radiologist, respectively, for the presence of myeloma bone disease. Blinded clinical and imaging data were reviewed by two haematologists in consensus and management recorded following clinical data ± 18F-FDG PET/CT or WBMRI. Bone disease was defined using International Myeloma Working Group (IMWG) criteria and a clinical reference standard. Per-patient sensitivity for lesion detection was established. McNemar test compared management based on clinical assessment ± 18F-FDG PET/CT or WBMRI. Results Sensitivity for bone lesions was 69.6% (32/46) for 18F-FDG PET/CT (54.3% (25/46) for PET component alone) and 91.3% (42/46) for WBMRI. 27/46 (58.7%) of cases were concordant. In 19/46 patients (41.3%) WBMRI detected more focal bone lesions than 18F-FDG PET/CT. Based on clinical data alone, 32/46 (69.6%) patients would have been treated. Addition of 18F-FDG PET/CT to clinical data increased this to 40/46 (87.0%) patients (p = 0.02); and WBMRI to clinical data to 43/46 (93.5%) patients (p = 0.002). The difference in treatment decisions was not statistically significant between 18F-FDG PET/CT and WBMRI (p = 0.08). Conclusion Compared to 18F-FDG PET/CT, WBMRI had a higher per patient sensitivity for bone disease. However, treatment decisions were not statistically different and either modality would be appropriate in initial staging, depending on local availability and expertise.

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