scholarly journals Metastatic prostate cancer with bone marrow infiltration mimicking multiple myeloma

2017 ◽  
Vol 6 (2) ◽  
pp. 269-273 ◽  
Author(s):  
Pankaj Mathur ◽  
Daisy Alapat ◽  
Manoj Kumar ◽  
Sharmilan Thanendrarajan
Keyword(s):  
Prostate Cancer ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Metastatic Prostate Cancer ◽  
Bone Marrow Infiltration

scholarly journals A case of metastatic prostate cancer and immune thrombocytopenia

2017 ◽  
Vol 24 (5) ◽  
pp. 434 ◽  
Author(s):  
D.M. Betsch ◽  
S. Gray ◽  
S.E. Zed
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Advanced Prostate Cancer ◽  
Immune Thrombocytopenia ◽  
Metastatic Prostate Cancer ◽  
Bone Marrow Involvement ◽  
Bone Marrow Infiltration ◽  
Advanced Malignancy ◽  
New Diagnosis

Prostate cancer frequently metastasizes to bone, but bone marrow involvement is relatively less common. In advanced prostate cancer, significant bone marrow infiltration can result in hematologic abnormalities such as anemia and thrombocytopenia. We report the case of a patient who presented with a new diagnosis of thrombocytopenia at the same time that he presented with prostate cancer metastatic to bone. He was found to have immune thrombocytopenia (itp) which responded to treatment with steroids. We discuss this case and review the literature on itp in the setting of advanced malignancy.

C-MYC Expression In Newly Diagnosed Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3156-3156
Author(s):  
Agoston Gyula Szabo ◽  
Anne Ortved Gang ◽  
Mette Ølgod Pedersen ◽  
Tim Svenstrup Poulsen ◽  
Tobias Wirenfeldt Klausen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cyclin D1 ◽  
B Cell Lymphoma ◽  
Response Rates ◽  
Primary Treatment ◽  
Bone Marrow Infiltration ◽  
World Health ◽  
Early Event ◽  
Newly Diagnosed

Abstract Background Overexpression of the c-MYC proto-oncogene plays an important role in the malignant phenotype of Burkitt lymphoma and diffuse large B cell lymphoma, but its role in multiple myeloma (MM) is controversial. Dysregulation of c-MYC, which is highly prevalent in human MM cell lines, is classically described as a late progression event. Translocations involving the c-MYC locus are reported to be present in approximately 13 % of newly diagnosed MM patients. However, a recent study showed expression of a MYC activation signature in 67 % of MM, and found c-MYC expression in 60 % of patients by immunohistochemistry (IHC). It has been suggested, that c-MYC expression is associated with the transition from monoclonal gammopathy of undetermined significance (MGUS) to MM, as an early event of MM pathogenesis, and that such a MYC addiction might have a useful therapeutic potential. However, the prevalence and the clinical associations of c-MYC expression among newly diagnosed MM patients need further assessment. Purpose We conducted a retrospective IHC study to evaluate the prevalence of c-MYC expression in newly diagnosed MM. Secondly, we wanted to assess, whether c-MYC expression was associated with factors known to influence prognosis, such as the patient’s clinical and laboratory features, end organ damage, International staging system (ISS) stage, and response to primary treatment. Thirdly, we wanted to assess, whether c-MYC expression was associated with known immunophenotypic variables in MM, such as CD20, Pax-5, Cyclin D1, and CD56. Material and methods Bone marrow aspirates from 119 patients diagnosed with MM from 2005-2010 were examined retrospectively. Tissue microarrays (TMAs) were constructed from formalin fixed, paraffin embedded samples using four 1mm cores from each patient sample. IHC was carried out with commercially available antibodies. Plasma cells were identified with anti-CD138 IHC. For detection of c-MYC, we used an anti-c-MYC rabbit monoclonal antibody obtained from Epitomics (Clone EP121). Samples were evaluated as c-MYC-positive, if at least 30 % of tumour cell nuclei were stained. Clinical data were obtained from the Danish Multiple Myeloma Database. Patients who received primary treatment (n=96) were examined separately based on whether they were treated with high-dose therapy (HDT) (n=31) or other treatment regimens (n=65). Response rates to primary treatment were evaluated. Associations between variables were assessed by calculating Fisher’s exact tests. Results The TMAs yielded sufficient material for assessment of c-MYC expression in 87 % of the study population. c-MYC expression was found in 44 (43 %) patients. At the time of diagnosis, c-MYC expression was significantly associated with the presence of extra-medullary myeloma (p = 0.026) and higher than the mean (36.6 %) bone marrow infiltration (p = 0.005). There were trends for c-MYC-positive patients to have World Health Organization (WHO) performance status 2 (p = 0.071) and hypercalcemia (p = 0.086). c-MYC expression was not associated with ISS stage, anemia, renal insufficiency or the evidence of bone disease. Among the patients who were not eligible for HDT, c-MYC expression had a trend to preclude achievement of complete response (CR) after primary treatment (p = 0.061). Only 5 patients achieved CR in this group, and all were c-MYC-negative. Such a trend was not found among patients who were treated with HDT, where c-MYC expression was not associated with specific response rates. Expression of CD20, Pax-5, Cyclin D1, and CD56 were found in 16 %, 38 %, 43 %, and 73 % of patients, respectively. c-MYC expression was not associated with any of the assessed immunophenotypic variables. Discussion and Conclusion c-MYC expression was found in almost half of newly diagnosed MM patients, which supports the theory that c-MYC activation is an early event in MM pathogenesis. c-MYC expression was associated with extra-medullary myeloma and high bone marrow infiltration, both factors known to have a negative effect on prognosis. Patient survival could not be evaluated in this cohort due to limited observation periods, but the results suggest that c-MYC expression should be studied further in patient cohorts with longer observation periods. Also, the mechanisms behind c-MYC expression should be addressed in future studies. c-MYC expression was not associated with the expression of CD20, Pax-5, Cyclin D1, or CD56. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Annexin II Interactions with the Annexin II Receptor Enhance Multiple Myeloma Cell Adhesion and Growth In the Bone Marrow Microenvironment

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 130-130 ◽  
Author(s):  
Sonia D'Souza ◽  
Noriyoshi Kurihara ◽  
Yusuke Shiozawa ◽  
Russell Taichman ◽  
Deborah Galson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Growth ◽  
Stromal Cells ◽  
Prostate Cancer Cell ◽  
Annexin Ii ◽  
Wild Type ◽  
Prostate Cancer Cells ◽  
Akt Phosphorylation

Abstract Abstract 130 Multiple myeloma (MM) is an incurable B-cell malignancy that develops in the bone marrow. The marrow microenvironment plays a critical role in supporting homing, lodging, and growth of MM cells by activating signaling pathways in both MM and bone marrow stromal cells (BMSC). Recently, we identified that annexin II (AXII) is involved in prostate cancer cell lodgment to the bone marrow as well as mobilization of prostate cancer cells to the peripheral blood. AXII expressed on stromal cells supports prostate cancer cell lodgment via the annexin II receptor (AXIIR) on prostate cancer cells. We hypothesized that MM cells use a similar mechanism to lodge and grow in the bone marrow. We demonstrated using bio-AXII, that MM cell lines and primary MM cells from 8 MM patients express the AXIIR protein. In addition, MM cells adhered significantly better to BMSC from wild-type mice than from AXII−/− mice. Knockdown of AXIIR by siRNA in MM.1S and ANBL.6 MM cells resulted in decreased AXII binding and decreased adherence of MM cells to KM101 stromal cells and BMSC from wild-type mice. Furthermore, the adhesion of MM.1SsiCon and MM.1SsiAXIIR cells to AXII−/− BMSC was similar indicating that AXII produced by MM cells does not act in an autocrine manner on attachment. Therefore, our studies indicate the importance of the interaction of AXII on BMSC with AXIIR on MM cells in adhesion. Our studies also revealed a role for AXIIR signaling on MM cell growth. We found that soluble AXII was released by osteoclasts into their conditioned media and stimulated the growth of MM cells via ERK1/2 and AKT phosphorylation in MM cells. AXII stimulation of MM cell growth was blocked by AXII antibody or by blocking ERK1/2 and AKT phosphorylation. In contrast, endogenous AXII produced by MM.1S cells did not stimulate MM.1S cell growth suggesting that autocrine AXII/AXIIR signaling in MM.1S cells does not contribute to MM.1S cell growth. Taken together, these results suggest that AXII/AXIIR axis in the myeloma microenvironment plays an important role in MM cell adhesion and growth through production of AXII by BMSC and osteoclasts. Disclosures: No relevant conflicts of interest to declare.

Use of whole-body diffusion-weighted magnetic resonance imaging for the diagnosis and therapeutic response of multiple myeloma

2014 ◽  
Vol 155 (31) ◽  
pp. 1241-1245
Author(s):  
Tamás Puskás ◽  
Imre Henits
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Magnetic Resonance ◽  
Functional Imaging ◽  
Bone Marrow Infiltration ◽  
Resonance Imaging ◽  
Diffusion Weighted ◽  
Weighted Magnetic Resonance Imaging ◽  
Weighted Sequences

Introduction: Multiple myeloma is an incurable neoplastic disorder of B cells characterized by diffuse bone marrow infiltration, circumscribed bone lesions, and soft-tissue spreading. The role of novel functional imaging techniques in multiple myeloma includes initial staging of the disease, detection and characterization of complications, and evaluation of the response to treatment. Aim: The authors present their 2 and a half-year experience with diffusion-weighted magnetic resonance imaging in staging and follow up of patients with multiple myeloma. Method: Conventional T1 weighted, T2 weighted fat suppressed and 2 b-values diffusion-weighted sequences were performed from skull base to symphysis in 27 patients suspected to have multiple myeloma. Apparent diffusion coefficient calculation was carried out in 3 cases. The final diagnosis of multiple myeloma was verified by bone-marrow biopsy. Results: In 13 cases magnetic resonance imaging revealed the suspected disease. In one patient magnetic resonance imaging failed to detect the disease because of metallic artifacts. In 6 cases diffusion-weighted sequences showed additional information about bone-marrow infiltration. Conclusions: Diffusion-weighted magnetic resonance imaging with conventional sequences is a useful and promising functional imaging modality in the early diagnosis of myeloma multiple. Orv. Hetil., 2014, 155(31), 1241–1245.

scholarly journals Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jeremy J. McGuire ◽  
Jeremy S. Frieling ◽  
Chen Hao Lo ◽  
Tao Li ◽  
Ayaz Muhammad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cancer Cells ◽  
Metastatic Prostate Cancer ◽  
Prostate Cancer Cell ◽  
Prostate Cancer Cells ◽  
Interleukin 28 ◽  
Selection Of

AbstractBone metastatic prostate cancer (PCa) promotes mesenchymal stem cell (MSC) recruitment and their differentiation into osteoblasts. However, the effects of bone-marrow derived MSCs on PCa cells are less explored. Here, we report MSC-derived interleukin-28 (IL-28) triggers prostate cancer cell apoptosis via IL-28 receptor alpha (IL-28Rα)-STAT1 signaling. However, chronic exposure to MSCs drives the selection of prostate cancer cells that are resistant to IL-28-induced apoptosis and therapeutics such as docetaxel. Further, MSC-selected/IL-28-resistant prostate cancer cells grow at accelerated rates in bone. Acquired resistance to apoptosis is PCa cell intrinsic, and is associated with a shift in IL-28Rα signaling via STAT1 to STAT3. Notably, STAT3 ablation or inhibition impairs MSC-selected prostate cancer cell growth and survival. Thus, bone marrow MSCs drive the emergence of therapy-resistant bone metastatic prostate cancer yet this can be disabled by targeting STAT3.

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