Bone marrow plasma macrophage inflammatory protein protein-1 alpha(MIP-1 alpha) and sclerostin in multiple myeloma: Relationship with bone disease and clinical characteristics

2014 ◽  
Vol 38 (5) ◽  
pp. 525-531 ◽  
Author(s):  
Xiao-Tao Wang ◽  
Yu-Chan He ◽  
Si-Yao Zhou ◽  
Jing-zi Jiang ◽  
Yu-Mei Huang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Disease ◽  
Clinical Characteristics ◽  
Inflammatory Protein ◽  
Bone Marrow Plasma ◽  
Macrophage Inflammatory Protein

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

2003 ◽  
Vol 123 (1) ◽  
pp. 106-109 ◽  
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

Immunoexpression of Macrophage Inflammatory Protein-1 Alpha on Bone Marrow Trephine Biopsies Correlates with the Extent of Bone Disease in Newly Diagnosed Patients with Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5119-5119
Author(s):  
Maria Roussou ◽  
Anna Tasidou ◽  
Efstathios Kastritis ◽  
Magdalini Migkou ◽  
Maria Gavriatopoulou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Disease ◽  
Newly Diagnosed ◽  
Santa Cruz ◽  
Myeloma Bone Disease ◽  
Inflammatory Protein ◽  
Lytic Lesions ◽  
Intermediate Expression ◽  
Macrophage Inflammatory Protein

Abstract Macrophage inflammatory protein-1 alpha (MIP-1alpha) is a low molecular weight chemokine that belongs to the RANTES family and is a potent osteoclast stimulator. Previous studies have shown that malignant plasma cells (PCs) from myeloma cell lines produce MIP-1alpha, while MIP-1alpha levels are elevated in the bone marrow plasma and the serum of patients with multiple myeloma (MM) and correlate with the extent of bone disease. The purpose of our study was to evaluate the role of MIP-1alpha immunoexpression on bone marrow trephine biopsies in myeloma bone disease and examine possible correlations between MIP-1alpha expression with survival and prognostic factors of MM. We evaluated formalin fixed paraffin-embedded bone marrow sections of 130 patients with newly diagnosed MM (66M/64F, median age: 68 years). Bone marrow sections were subjected to immunohistochemistry study using the anti-MIP- 1alpha monoclonal antibody (Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA). The immunoreactivity of MIP-1alpha was examined on the basis of positive PCs with the following cut off values: <20% positive PCs (negative expression group, group I), 20–50% positive PCs (intermediate expression group, group II) and >50% positive PCs (high expression group, group III). Moreover MIP-1alpha was measured using ELISA methodology (R&D Systems, Minneapolis, MN, USA) in the serum of the patients. The extent of bone disease was assessed radiographically, and grading was performed as follows: group A included 43 patients (33%) who had no lytic lesions and/or osteoporosis only, group B included 24 patients (18%) who had lytic lesions in 1–3 areas, whereas group C included 63 patients (48%) with lytic lesions in >3 areas and/or a bone fracture. Thirty-seven (28%) patients had negative MIP-1alpha expression, 17 (13%) intermediate expression and 79 (59%) high expression of MIP-1alpha. MIP-1alpha expression of ≥20% PCs in the trephine biopsies significantly correlated with the extent of bone disease (Figure 1, ANOVA p<0.0001). Furthermore, 91 patients (70%) had values of serum MIP-1alpha >14 pg/ml, which was the median value observed in 20 controls of similar age and gender (p<0.001). MIP-1alpha serum levels also correlated with the extent of bone disease (ANOVA p<0.0001). In terms of overall survival, no significant association was observed in relation to MIP-1alpha expression. Increased immunoexpression of MIP-1alpha was associated with high plasma cell infiltration in the bone marrow (r=0.348, p<0.0001), low platelet count (r=0.282; p=0.0012), hypercalcemia (r=0.246; p=0.022), elevated serum creatinine (r=0.258, p=0.027), and advanced disease stage (ISS, p=0.034). Our findings underline, for the first time, the increased incidence of high immunoexpression of MIP-1alpha in the malignant PCs of myeloma patients and the correlation between the expression of MIP-1alpha by myeloma PCs in the trephine biopsies and the extent of lytic bone disease. These results confirm the significant role of MIP-1alpha in the pathogenesis of myeloma bone disease and suggest that MIP-1alpha may represent a rational therapeutic target for the management of bone destruction in myeloma. Figure Figure

Brain-Derived Neurotrophic Factor Is a Potential Osteoclast Stimulatory Factor In Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1917-1917
Author(s):  
Chun-Yan Sun ◽  
Yu Hu ◽  
Xiao-Mei She ◽  
You Qin ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Disease ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Osteoclast Formation ◽  
Bone Lesions ◽  
Bone Marrow Plasma

Abstract Abstract 1917 Background and Objective: Multiple myeloma (MM) is characterized by accumulation of monoclonal plasma cells in the bone marrow and progression of lytic bone lesions. The mechanisms of enhanced bone resorption in patients with myeloma are not fully defined. We have previously identified the role of brain-derived neurotrophic factor (BDNF) in proliferation and migration of MM cells. In the present study, we investigated whether BDNF was present in marrow from patients with MM and possibly involved in MM cell-induced osteolysis. Methods and Results: Levels of bone marrow plasma BDNF was measured by ELISA in a cohort of individuals with MM and controls. The concentration of BDNF was found to be significantly elevated in patients with MM (879 ± 93) pg/ml when compared with bone marrow plasma derived from normal control subjects (186 ± 52) pg/ml (p < 0.001). Moreover, bone marrow plasma levels of BDNF positively correlated with plasma cell burden and extent of bone disease in MM patients. In osteoclast formation assay, bone marrow plasma from 31 of 37 patients with MM tested significantly stimulated the formation of osteoclast when compared to controls (61.8 ± 7 [mean ± SEM for the 31 patients] versus 25.2 ± 6 TRAP+ multinucleated cells/well [mean ± SEM for the 12 controls]; p < 0.01). The effect was significantly blocked by a neutralizing antibody to BDNF (p < 0.05), suggesting a critical role for BDNF in osteoclast activation. Furthermore, BDNF was found to dose-dependently increased the formation of multinucleated, TRAP+ osteoclast. The direct effects of recombinant BDNF on osteoclast formation and bone resorption support the potential role of BDNF in the MM bone disease. Using reverse-transcriptase polymerase chain reaction analysis and western blotting assay, we demonstrated that BDNF receptor TrkB was expressed by human osteoclast precursors and a Trk inhibitor K252a markedly inhibited osteoclast formation stimulated with BDNF. These data suggested that TrkB is the functional receptor mediating BDNF's effect on osteoclast formation. Finally, bone marrow plasma BDNF level positively correlated with macrophage inflammatory protein (MIP)-1α (r = 0.45, p < 0.005) and receptor activator of nuclear factor-κB ligand (RANKL) (r = 0.68, p < 0.0001), two major osteoclast stimulatory factors in MM. Conclusion: Taken together, our results demonstrate the ability of MM cells to secret BDNF correlates with the severity of osteoclastic bone resorption, and provide evidence that BDNF play a causal role in the development of MM bone lesions through TrkB receptor. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Bone Marrow Plasma Cytokine Signature Profiles in Severe Aplastic Anemia

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Bingnan Liu ◽  
Yuanyuan Shao ◽  
Zixuan Liu ◽  
Chunyan Liu ◽  
Tian Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Aplastic Anemia ◽  
Healthy People ◽  
Severe Aplastic Anemia ◽  
Colony Stimulating Factor ◽  
Inflammatory Protein ◽  
Bone Marrow Plasma ◽  
Macrophage Inflammatory Protein ◽  
Stimulating Factor

Objective. We studied bone marrow plasma (BMP) cytokines in severe aplastic anemia (SAA) patients and healthy volunteers to investigate differences in the cytokine profiles between them and propose a cytokine signature of SAA. Methods. A Bio-Plex suspension array system was used to measure 27 analytes in BMP samples from 47 SAA patients and 30 healthy donors. Results. Compared to healthy people, SAA patients had higher levels of tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), monocyte chemoattractant protein 1 (MCP-1), and granulocyte colony-stimulating factor (G-CSF). They also had lower levels of interleukin-1 receptor antagonist (IL-1ra), interleukin-9 (IL-9), regulated upon activation normal T cell expressed and secreted (RANTES) factor, platelet-derived growth factor-BB (PDGF-BB), and macrophage inflammatory protein 1β (MIP-1β). Levels of interleukin-4 (IL-4), IL-1ra, macrophage inflammatory protein 1α (MIP-1α), and eotaxin were significantly higher in recovering SAA (RSAA) patients. Levels of IL-5, IL-6, IL-10, IL-12, IL-13, IL-15, granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) were undetectable. There were no significant differences in the levels of IL-1β, IL-4, IL-7, IL-8, IL-17, basic fibroblast growth factor (FGF-β), and IFN inducible protein-10 (IP-10) between patients and healthy controls (HCs). Eotaxin, IL-1ra, MCP-1, MIP-1β, and RANTES levels increased after IST, whereas IFN-γ, G-CSF, IL-2, IL-7, and TNF-α levels decreased after IST. Conclusions. The current study demonstrated distinct cytokine profiles among untreated SAA patients, recovering SAA (RSAA) patients, and healthy people. The cytokines of RSAA patients showed similar characteristics to those of untreated SAA patients and healthy people, respectively, which may reflect that the immune status of RSAA patients is in different stages of recovery after IST; thus, it may provide an important tool in diagnosing and evaluating or predicting curative effects in clinics.

Bone disease as the first manifestation of systemic AL-amyloidosis

2020 ◽  
Vol 92 (7) ◽  
pp. 85-89
Author(s):  
L. P. Mendeleeva ◽  
I. G. Rekhtina ◽  
A. M. Kovrigina ◽  
I. E. Kostina ◽  
V. A. Khyshova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Disease ◽  
Plasma Cells ◽  
Interventricular Septum ◽  
Bone Destruction ◽  
Amyloid Deposition ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Linear Type

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.

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

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
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.

scholarly journals Multiple myeloma: circulating lymphocytes that express plasma cell antigens

Blood ◽  
1984 ◽  
Vol 64 (2) ◽  
pp. 352-356
Author(s):  
GJ Ruiz-Arguelles ◽  
JA Katzmann ◽  
PR Greipp ◽  
NJ Gonchoroff ◽  
JP Garton ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Peripheral Blood Lymphocytes ◽  
Tumor Burden ◽  
B Cell Differentiation ◽  
Blood Lymphocytes ◽  
Bone Marrow Plasma

The bone marrow and peripheral blood of 14 patients with multiple myeloma were studied with murine monoclonal antibodies that identify antigens on plasma cells (R1–3 and OKT10). Peripheral blood lymphocytes expressing plasma cell antigens were found in six cases. Five of these cases expressed the same antigens that were present on the plasma cells in the bone marrow. Patients that showed such peripheral blood involvement were found to have a larger tumor burden and higher bone marrow plasma cell proliferative activity. In some patients, antigens normally found at earlier stages of B cell differentiation (B1, B2, and J5) were expressed by peripheral blood lymphocytes and/or bone marrow plasma cells.

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