scholarly journals Microfluidic Device Engineered to Study the Trafficking of Multiple Myeloma Cancer Cells Through the Sinusoidal Niche of Bone Marrow

2021 ◽  
Author(s):  
Chao Sui ◽  
Jenny Zilberberg ◽  
Woo Lee
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cancer Cells ◽  
Microfluidic Device ◽  
Plasma Cells ◽  
Bm Niche ◽  
B Cell Malignancy ◽  
Sinusoidal Endothelium ◽  
Integral Element ◽  
Sinusoidal Flow

Abstract Multiple myeloma (MM) is an incurable B cell malignancy characterized by the accumulation of monoclonal abnormal plasma cells in the bone marrow (BM). It has been a significant challenge to study the spatiotemporal interactions of MM cancer cells with the embedded microenvironments of BM. Here we report a microfluidic device which was designed to mimic several physiological features of the BM niche: (1) sinusoidal circulation, (2) sinusoidal endothelium, and (3) stroma. The endothelial and stromal compartments were constructed and used to demonstrate the device’s utility by spatiotemporally characterizing the CXCL12-mediated egression of MM cells from the BM stroma and its effects on the barrier function of endothelial cells (ECs). We found that the egression of MM cells resulted in less organized and loosely connected ECs, the widening of EC junction pores, and increased permeability through ECs, but without significantly affecting the number density of viable ECs. The results suggest that the device can be used to study the physical and secreted factors determining the trafficking of cancer cells through BM. The sinusoidal flow feature of the device provides an integral element for further creating systemic models of cancers that reside or metastasize to the BM niche.

scholarly journals Bone Marrow Microenvironment in Multiple Myeloma Progression

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
S. Manier ◽  
A. Sacco ◽  
X. Leleu ◽  
I. M. Ghobrial ◽  
A. M. Roccaro
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Plasma Cells ◽  
Cellular Compartment ◽  
Cell Homing ◽  
Premetastatic Niche ◽  
Bm Niche ◽  
Malignant Plasma Cell ◽  
Made In

Substantial advances have been made in understanding the biology of multiple myeloma (MM) through the study of the bone marrow (BM) microenvironment. Indeed, the BM niche appears to play an important role in differentiation, migration, proliferation, survival, and drug resistance of the malignant plasma cells. The BM niche is composed of a cellular compartment (stromal cells, osteoblasts, osteoclasts, endothelial cells, and immune cells) and a noncellular compartment including the extracellular matrix (ECM) and the liquid milieu (cytokines, growth factors, and chemokines). In this paper we discuss how the interaction between the malignant plasma cell and the BM microenvironment allowed myeloma progression through cell homing and the new concept of premetastatic niche.

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 An Unprecedented Case of p190 BCR-ABL Chronic Myeloid Leukemia Diagnosed during Treatment for Multiple Myeloma: A Case Report and Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Kosuke Miki ◽  
Naoshi Obara ◽  
Kenichi Makishima ◽  
Tatsuhiro Sakamoto ◽  
Manabu Kusakabe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Plasma Cells ◽  
Bone Marrow Examination ◽  
Bone Lesions ◽  
Dexamethasone Treatment ◽  
Lytic Bone Lesions

We report the case of a 76-year-old man who was diagnosed as having chronic myeloid leukemia (CML) with p190 BCR-ABL while receiving treatment for symptomatic multiple myeloma (MM). The diagnosis of MM was based on the presence of serum M-protein, abnormal plasma cells in the bone marrow, and lytic bone lesions. The patient achieved a partial response to lenalidomide and dexamethasone treatment. However, 2 years after the diagnosis of MM, the patient developed leukocytosis with granulocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed Philadelphia chromosomes and chimeric p190 BCR-ABL mRNA. Fluorescence in situ hybridization also revealed BCR-ABL-positive neutrophils in the peripheral blood, which suggested the emergence of CML with p190 BCR-ABL. The codevelopment of MM and CML is very rare, and this is the first report describing p190 BCR-ABL-type CML coexisting with MM. Moreover, we have reviewed the literature regarding the coexistence of these diseases.

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.

scholarly journals The Evolution in The Treatment of Multiple Myeloma Towards Targeted Magnetic Molecularly Imprinted Nanomedicines

2015 ◽  
pp. 1-2
Author(s):  
Edgar Pérez-Herrero
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bacterial Infections ◽  
Plasma Cells ◽  
The Body ◽  
Western World ◽  
Bone Lesions ◽  
Non Hodgkin Lymphoma ◽  
Clonal Proliferation ◽  
Tract Infections

Multiple myeloma is the second more frequently haematological cancer in the western world, after non-Hodgkin lymphoma, being about the 1-2 % of all the cancers cases and the 10-13% of hematologic diseases. The disease is caused by an uncontrolled clonal proliferation of plasma cells in the bone marrow that accumulate in different parts of the body, usually in the bone marrow, around some bones, and rarely in other tissues, forming tumor deposits, called plasmocytomas. This uncontrolled clonal proliferation of plasma cells produces the secretion of an abnormal monoclonal immunoglobulin (paraprotein or M-protein) and prevents the formation of the other antibodies produced by the normal plasma cells that are destroyed. The anormal secretion of paraproteins unbalance the osteoblastosis and osteoclastosis processes, leading to bone lesions that cause lytic bone deposits and the release of calcium from bones (hypercalcemia) that may produce renal failure. Regions affected by bone lesions are the skull, spine, ribs, sternum, pelvis and bones that form part of the shoulders and hips. The substitution of the healthy bone marrow by infiltrating malignant cells and the inhibition of the normal production of red blood cells produce anaemia, thrombocytopenia and leukopenia. Multiple myeloma patients are immunosuppressed because of leukopenia and the abnormal immunoglobulin production caused by the uncontrolled clonal proliferation of plasma cells, being susceptible to bacterial infections, like pneumonias and urinary tract infections. The interaction of immunoglobulin with hemostatic mechanisms may lead to haemorrhagic diathesis or thrombosis. Also, disorders of the central and peripheral nervous system are part of the disease, being the more common neurological manifestations the spinal cord compressions and the peripheral neuropathies.

scholarly journals Multiple Myeloma with Suspected Non-Secretory Type

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Annisa Ginar Indrarsi ◽  
Usi Sukorini
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Protein Electrophoresis ◽  
Palpebral Conjunctiva ◽  
General Weakness ◽  
M Spike ◽  
G Ratio

Multiple Myeloma (MM) is a hematological malignancy characterized by clonal plasma cell in bone marrow that produceabnormal globulin, which resulted in monoclonal gammopathy. Multiple Myeloma Non-Secretory (MMNS) is a very rareform of multiple myeloma with monoclonal plasmocytic proliferation in bone marrow supported by clinical manifestationand radiological findings. However, plasma cells fail to secrete immunoglobulin. A 44-year-old female came to SardjitoGeneral Hospital with main complaints of weakness and back pain. General weakness and pale palpebral conjunctiva were6 observed (+/+), liver and spleen were not palpable. Blood test results were as follows: Hb 3.0 g/dL, RBC 1.07 x 10 / μL, WBC3 3 562 x 10 /μL, PLT 114 x 10 /μL, A/G ratio 1.07, BUN 51.5 mg/dL, creatinine 4.62 mg/dL, and calcium 3.1 mmol/L. Skeletalsurvey suggested a multiple osteolytic. Protein electrophoresis revealed hypogammaglobulinemia with no M-spike. Therewere 66% of plasma cells in bone marrow. Patient was diagnosed by MMNS. Diagnosis MMNS can be established if clonalplasmacytes is accompanied with renal insufficiency and hypercalcemia. However, monoclonal gammopathy was not foundin serum protein electrophoresis. A case reported of 44-year-old female diagnosed as MMNS with 'punched out' multipleosteolytic, increased plasma cells in bone marrow without evidence of paraprotein in circulation proved by low A/G ratio andnegative M-spike.

Sign in / Sign up

Export Citation Format

Share Document