Browsing by Subject "Plasmacytoma"

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    CD166 modulates disease progression and osteolytic disease in multiple myeloma
    (2016-03-16) Xu, Linlin; Xu, Linlin
    Multiple myeloma (MM) is an incurable malignancy characterized by the proliferation of neoplastic plasma cells in the bone marrow (BM) and by multiple osteolytic lesions throughout the skeleton. We previously reported that CD166 is a functional molecule on normal hematopoietic stem cells (HSC) that plays a critical role in HSC homing and engraftment, suggesting that CD166 is involved in HSC trafficking and lodgment. CD166, a member of the immunoglobulin superfamily capable of mediating homophilic interactions, has been shown to enhance metastasis and invasion in several tumors. However, whether CD166 is involved in MM and plays a role in MM progression has not been addressed. We demonstrated that a fraction of all human MM cell lines tested and MM patients’ BM CD138+ cells express CD166. Additionally, CD166+ cells preferentially home to the BM of NSG mice. Knocking-down (KD) CD166 expression on MM cells with shRNA reduced their homing to the BM. Furthermore, in a long-term xenograft model, NSG mice inoculated with CD166KD cells showed delayed disease progression and prolonged survival compared to mice receiving mock transduced cells. To examine the potential role of CD166 in osteolytic lesions, we first used a novel Ex Vivo Organ Culture Assay (EVOCA) which creates an in vitro 3D system for the interaction of MM cells with the bone microenvironment. EVOCA data from MM cells lines as well as from primary MM patients’ CD138+ BM cells demonstrated that bone osteolytic resorption was significantly reduced when CD166 was absent on MM cells or calvarial cells. We then confirmed our ex vivo findings with intra-tibial inoculation of MM cells in vivo. Mice inoculated with CD166KD cells had significantly less osteolytic lesions. Further analysis demonstrated that CD166 expression on MM cells alters bone remodeling by inhibiting RUNX2 gene expression in osteoblast precursors and increasing RANKL to OPG ratio in osteoclast precursors. We also identified that CD166 is indispensable for osteoclastogenesis via the activation of TRAF6-dependent signaling pathways. These results suggest that CD166 directs MM cell homing to the BM and promotes MM disease progression and osteolytic disease. CD166 may serve as a therapeutic target in the treatment of MM.
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    Multiple myeloma causing interstitial pulmonary infiltrates and soft-tissue plasmacytoma
    (Elsevier, 2018-05-19) Lok, Ryan; Golovyan, Dmitriy; Smith, Joseph; Medicine, School of Medicine
    Multiple Myeloma (MM) is a relatively rare disease and MM presenting outside the bone marrow, known as extramedullary myeloma (EMM), is rarer still. While the liver and CNS are most commonly affected in EMM, the lung parenchyma is an especially unusual site of involvement. We present the case of a 64-year-old male with known history of MM admitted with acute respiratory failure and a chest wall mass. Chest CT revealed patchy interstitial and alveolar opacities with no pulmonary masses or nodules. Bronchoalveolar lavage (BAL) was performed, with flow cytometry demonstrating monoclonal plasma cells expressing CD38, CD138 and CD56 with lambda light chain restriction. Fine Needle Aspiration of chest wall mass revealed CD138-positive cells as well. Review of the literature revealed only one other documented case of a patient presenting with both interstitial lung parenchymal involvement with MM as well as soft tissue plasmacytoma, with this occurring in a patient who had previously underwent stem cell transplant. To our knowledge, we report the first recorded case of this presentation in a patient without a history of stem cell transplantation. Furthermore, it demonstrates the utility of using BAL, rather than lung biopsy, to establish the diagnosis through less invasive means.