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T cell myeloma

Jordan Senchak, Peter Pickens
We present an 88-year-old male with simultaneous T-cell prolymphocytic leukemia and stable smoldering myeloma with excellent initial response to three months of alemtuzumab. The patient relapsed at twelve months with severe cutaneous disease. Biopsy of a representative plaque demonstrated CD30 positivity in rare malignant lymphocytes. The patient demonstrated no response to reintroduction with a full course of alemtuzumab. He was therefore treated with brentuximab vedotin, resulting in partial remission of skin involvement that persisted for three months...
September 28, 2016: Hematology Reports
Kazuhito Suzuki, Shingo Yano, Kaichi Nishiwaki, Koji Sano, Takaki Shimada, Yuichi Yahagi, Yoji Ogasawara, Katsuki Sugiyama, Shinobu Takahara, Takeshi Saito, Kinuyo Kasama, Jiro Minami, Hiroki Yokoyama, Yutaro Kamiyama, Atsushi Katsube, Hidekazu Masuoka, Mitsuji Katori, Tomohito Machishima, Aya Ouchi, Nobuaki Dobashi, Ken Kaito, Noriko Usui, Keisuke Aiba
The clinical features and prognostic significance of myeloma cells containing granules remain unclear. The purpose of this retrospective study was to investigate the clinical significance of granule-containing myeloma cells in patients with newly diagnosed multiple myeloma (NDMM). We retrospectively analyzed the records of 122 patients diagnosed with NDMM between January 2007 and December 2013. Granule-containing myeloma cells were defined as myeloma cells that exhibited three or more granules in their cytoplasm by May-Giemsa staining...
October 13, 2016: Cancer Medicine
E Terpos, D Christoulas, E Kastritis, T Bagratuni, M Gavriatopoulou, M Roussou, A Papatheodorou, E Eleutherakis-Papaiakovou, N Kanellias, C Liakou, I Panagiotidis, M Migkou, P Kokkoris, L A Moulopoulos, M A Dimopoulos
Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls...
October 7, 2016: Blood Cancer Journal
Thomas Greuter, Martin Browne, Corina Dommann-Scherrer, Daniel Binder, Christoph Renner, Ursula Kapp
In the present study, the case of a 41-year-old man with immunoglobulin (Ig)M multiple myeloma (MM) that presented with an unusually non-aggressive clinical course who has survived for >9 years to date, is presented. Initial diagnosis of symptomatic MM was established according to the International Myeloma Working Group consensus statement and guidelines. Due to the mild symptoms, no therapy was administered and the patient was closely followed up. Eight years after initial diagnosis, clinical, morphological and genetic progression occurred with the development of hypercalcemia, progressively deteriorating polyneuropathy, clonal expansion of plasma cells up to 50% of hematopoietic cells and demonstration of the typical t(11;14) translocation (Ig heavy chain locus rearrangement)...
October 2016: Oncology Letters
Susan J Lee, Ivan Borrello
Multiple myeloma (MM) is a hematologic cancer derived from malignant plasma cells within the bone marrow. Unlike most solid tumors, which originate from epithelial cells, the myeloma tumor is a plasma cell derived from the lymphoid cell lineage originating from a post-germinal B-cell. As such, the MM plasma cell represents an integral component of the immune system in terms of both antibody production and antigen presentation, albeit not efficiently. This fundamental difference has significant implications when one considers the implications of immunotherapy...
2016: Cancer Treatment and Research
Michele Moschetta, Yawara Kawano, Klaus Podar
Unprecedented advances in multiple myeloma (MM) therapy during the last 15 years are predominantly based on our increasing understanding of the pathophysiologic role of the bone marrow (BM) microenvironment. Indeed, new treatment paradigms, which incorporate thalidomide, immunomodulatory drugs (IMiDs), and proteasome inhibitors, target the tumor cell as well as its BM microenvironment. Ongoing translational research aims to understand in more detail how disordered BM-niche functions contribute to MM pathogenesis and to identify additional derived targeting agents...
2016: Cancer Treatment and Research
Salomon Manier, Karma Salem, Siobhan V Glavey, Aldo M Roccaro, Irene M Ghobrial
Multiple myeloma (MM) is a genetically complex disease. The past few years have seen an evolution in cancer research with the emergence of next-generation sequencing (NGS), enabling high throughput sequencing of tumors-including whole exome, whole genome, RNA, and single-cell sequencing as well as genome-wide association study (GWAS). A few inherited variants have been described, counting for some cases of familial disease. Hierarchically, primary events in MM can be divided into hyperdiploid (HDR) and nonhyperdiploid subtypes...
2016: Cancer Treatment and Research
Hermann Einsele, Martin Schreder
Elotuzumab is a humanized monoclonal antibody targeting the extracellular domain of signaling lymphocytic activation molecule F7 (SLAMF7) highly expressed in multiple myeloma cells. Upon binding to myeloma cells, elotuzumab exerts its cytotoxic effects through antibody-dependent cellular cytotoxicity, the antibody-induced selective lysis of tumor cells by activated natural killer (NK) cells. Furthermore, elotuzumab has been shown to directly induce NK-cell activation by binding to SLAMF7 expressed on NK cells and to indirectly modulate T-cell function by promoting the secretion of cytokines from NK cells...
October 2016: Therapeutic Advances in Hematology
Emily A Lanzel, M Paula Gomez Hernandez, Amber M Bates, Christopher N Treinen, Emily E Starman, Carol L Fischer, Deepak Parashar, Janet M Guthmiller, Georgia K Johnson, Taher Abbasi, Shireen Vali, Kim A Brogden
PURPOSE: Interaction of the programmed death-1 (PD-1) co-receptor on T cells with the programmed death-ligand 1 (PD-L1) on tumor cells can lead to immunosuppression, a key event in the pathogenesis of many tumors. Thus, determining the amount of PD-L1 in tumors by immunohistochemistry (IHC) is important as both a diagnostic aid and a clinical predictor of immunotherapy treatment success. Because IHC reactivity can vary, we developed computational simulation models to accurately predict PD-L1 expression as a complementary assay to affirm IHC reactivity...
September 29, 2016: Cancer Immunology, Immunotherapy: CII
E Müller, S Bauer, T Stühmer, A Mottok, C-J Scholz, T Steinbrunn, D Brünnert, A Brandl, H Schraud, S Kreßmann, A Beilhack, A Rosenwald, R C Bargou, M Chatterjee
Direct therapeutic targeting of oncogenic RAS is currently still impossible due to lack of suitable pharmacological inhibitors. Because specific blockade of druggable RAS effectors might represent an alternative treatment approach, we evaluated the role of the Raf complex for multiple myeloma (MM) pathobiology. We found frequent overexpression of the Raf isoforms (A-, B- and C-Raf) and downstream activation of MEK1,2/ERK1,2 in MM cells. Concomitant inhibition of all Raf isoforms (pan-Raf inhibition) by RNAi or pharmacological inhibitors was required to strongly induce apoptosis in MM cell lines, primary MM cells in vitro, and in a syngeneic MM mouse model in vivo...
September 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Timothy N Trotter, Justin T Gibson, Tshering Lama Sherpa, Pramod S Gowda, Deniz Peker, Yang Yang
Multiple myeloma (MM) cells reside in the bone marrow microenvironment and form complicated interactions with nonneoplastic, resident stromal cells. We previously found that aggressive MM cells shift osteoblast progenitors toward adipogenesis. In addition, adipocytes are among the most common cell types in the adult skeleton; both mature adipocytes and preadipocytes serve as endocrine cells that secrete a number of soluble molecules into the microenvironment. Therefore, we used a combination of in vivo and in vitro methods to test the hypothesis that an increase in adipocyte lineage cells feeds back to promote MM progression...
September 17, 2016: American Journal of Pathology
Chunming Gu, Tianfu Li, Zhao Yin, Shengting Chen, Jia Fei, Jianping Shen, Yuan Zhang
Berberine (BBR), a traditional Chinese herbal medicine compound, has emerged as a novel class of anti-tumor agent. Our previous microRNA (miRNA) microarray demonstrated that miR-106b/25 was significantly down-regulated in BBR-treated multiple myeloma (MM) cells. Here, systematic integration showed that miR-106b/25 cluster is involved in multiple cancer-related signaling pathways and tumorigenesis. MiREnvironment database revealed that multiple environmental factors (drug, ionizing radiation, hypoxia) affected the miR-106b/25 cluster expression...
September 19, 2016: Functional & Integrative Genomics
T Jelinek, E Kryukova, Z Kufova, F Kryukov, R Hajek
Proteasome inhibitors are the backbone in the treatment of multiple myeloma with 3 of its representatives (bortezomib, carfilzomib, and ixazomib) having already been approved. There is a different situation altogether in the treatment of amyloid light chain (AL) amyloidosis where owing to the rarity of this entity neither of these drugs has currently gained approval. Amyloid light chain plasma cells are possibly more vulnerable to bortezomib than myeloma plasmocytes because of a slightly distinct mechanism of action, which is described in depth in this manuscript...
September 20, 2016: Hematological Oncology
P Roy, T Mukherjee, B Chatterjee, B Vijayaragavan, B Banoth, S Basak
Environmental drug resistance constitutes a serious impediment for therapeutic intervention in multiple myeloma. Tumor-promoting cytokines, such as tumor necrosis factor (TNF), induce nuclear factor-κB (NFκB)- driven expression of pro-survival factors, which confer resistance in myeloma cells to apoptotic insults from TNF-related apoptosis-inducing ligand (TRAIL) and other chemotherapeutic drugs. It is thought that RelA:p50 dimer, activated from IκBα-inhibited complex in response to TNF-induced canonical NFκB signal, mediates the pro-survival NFκB function in cancerous cells...
September 19, 2016: Oncogene
Saad S Kenderian, David L Porter, Saar Gill
Hematopoietic cell transplantation (HCT) remains an important and potentially curative option for most hematologic malignancies. As a form of immunotherapy, allogeneic HCT (allo-HCT) offers the potential for durable remissions but is limited by transplantation- related morbidity and mortality owing to organ toxicity, infection, and graft-versus-host disease. The recent positive outcomes of chimeric antigen receptor T (CART) cell therapy in B cell malignancies may herald a paradigm shift in the management of these disorders and perhaps other hematologic malignancies as well...
September 13, 2016: Biology of Blood and Marrow Transplantation
Kristina Berg Lorvik, Clara Hammarstrom, Marte Fauskanger, Ole Audun Werner Haabeth, Michael Zangani, Guttorm Haraldsen, Bjarne Bogen, Alexandre Corthay
Adoptive cell therapy (ACT) trials to date have focused on transfer of autologous tumor-specific cytotoxic CD8+ T cells, however, the potential of CD4+ T helper (Th) cells for ACT is gaining interest. While encouraging results have been reported with interferon-γ (IFNγ)-producing Th1 cells, tumor-specific Th2 cells have been largely neglected for ACT due to their reported tumor-promoting properties. In this study, we tested the efficacy of idiotype-specific Th2 cells for the treatment of mice with Major Histocompatibility Complex (MHC) class II-negative myeloma...
September 12, 2016: Cancer Research
Anders Tveita, Marte Fauskanger, Bjarne Bogen, Ole Audun Werner Haabeth
CD4+ T cells have been shown to reject tumor cells with no detectable expression of major histocompatibility complex class II (MHC II). However, under certain circumstances, induction of ectopic MHC II expression on tumor cells has been reported.To confirm that CD4+ T cell-mediated anti-tumor immunity can be successful in the complete absence of antigen display on the tumor cells themselves, we eliminated MHC II on tumor cells using CRISPR/Cas9. Our results demonstrate that ablation of the relevant MHC II (I-Ed) in multiple myeloma cells (MOPC315) does not hinder rejection by tumor-specific CD4+ T cells...
September 10, 2016: Oncotarget
Boyan Fang, Andrew McKeon, Shannon R Hinson, Thomas J Kryzer, Sean J Pittock, Allen J Aksamit, Vanda A Lennon
Importance: A novel astrocytic autoantibody has been identified as a biomarker of a relapsing autoimmune meningoencephalomyelitis that is immunotherapy responsive. Seropositivity distinguishes autoimmune glial fibrillary acidic protein (GFAP) meningoencephalomyelitis from disorders commonly considered in the differential diagnosis. Objective: To describe a novel IgG autoantibody found in serum or cerebrospinal fluid that is specific for a cytosolic intermediate filament protein of astrocytes...
September 12, 2016: JAMA Neurology
M S Dal, A Doğan, A Karakuş, T Dal, M Kaya, O Ayyıldız
A 58-year-old female patient whose serological test results were Hepatitis B surface antigen (HBsAg) negative and Hepatitis B surface antibody (HBsAb) positive, diagnosed with Multiple myeloma. Autologous haematopoietic stem-cell transplantation was subsequently performed after induction chemotherapy. One-year later the patient was diagnosed as Hepatitis B Virus (HBV) reactivation and was started on lamivudine oral therapy. Hepatitis B surface antigen (HBsAg) negative is negative and HBsAb is positive in patients scheduled for chemotherapy, HBV DNA levels should still be investigated...
February 22, 2016: West Indian Medical Journal
Gabriela Rozic, Lena Paukov, Jana Jakubikova, Dikla Ben-Shushan, Adrian Duek, Adi Leiba, Abraham Avigdor, Arnon Nagler, Merav Leiba
Despite advances in treatment, multiple myeloma (MM) remains incurable. Here we propose the use of STK405759, a novel microtubule targeting agent (MTA) and member of the furan metotica family for MM therapy.STK405759 inhibited tubulin polymerization in a cell-free system and in myeloma cells. This molecule had potent cytotoxic activity against several MM cell lines and patient-derived MM cells. Moreover, STK405759 demonstrated cytotoxicity against drug-resistant myeloma cells that overexpressed the P-glycoprotein drug-efflux pump...
August 23, 2016: Oncotarget
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