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Plasma cell myeloma

Anubha Gupta, Pramit Mallick, Ojaswa Sharma, Ritu Gupta, Rahul Duggal
Plasma cell segmentation is the first stage of a computer assisted automated diagnostic tool for multiple myeloma (MM). Owing to large variability in biological cell types, a method for one cell type cannot be applied directly on the other cell types. In this paper, we present PCSeg Tool for plasma cell segmentation from microscopic medical images. These images were captured from bone marrow aspirate slides of patients with MM. PCSeg has a robust pipeline consisting of a pre-processing step, the proposed modified multiphase level set method followed by post-processing steps including the watershed and circular Hough transform to segment clusters of cells of interest and to remove unwanted cells...
2018: PloS One
Renato Zambello, Filippo Crimì, Albana Lico, Gregorio Barilà, Antonio Branca, Annamaria Guolo, Cristiano Varin, Roberto Vezzaro, Lucia Checuz, Vanna Scapin, Tamara Berno, Marco Pizzi, Alberto Ponzoni, Ercole De Biasi, Stefania Vio, Gianpietro Semenzato, Pietro Zucchetta, Carmelo Lacognata
We evaluated differences in density and 18 F-FDG PET/MRI features of lytic bone lesions (LBLs) identified by whole-body low-dose CT (WB-LDCT) in patients affected by newly diagnosed multiple myeloma (MM). In 18 MM patients, 135 unequivocal LBLs identified by WB-LDCT were characterized for inner density (negative or positive Hounsfield unit (HU)), where negative density (HU < 0) characterizes normal yellow marrow whereas positive HU correlates with tissue-like infiltrative pattern. The same LBLs were analyzed by 18 F-FDG PET/DWI-MRI, registering DWI signal with ADC and SUV max values...
December 11, 2018: Annals of Hematology
Stefania Oliva, Rossella Troia, Mattia D'Agostino, Mario Boccadoro, Francesca Gay
In the biology of multiple myeloma (MM), immune dysregulation has emerged as a critical component for novel therapeutic strategies. This dysfunction is due to a reduced antigen presentation, a reduced effector cell ability and a loss of reactive T cells against myeloma, together with a bone marrow microenvironment that favors immune escape. The Programmed Death-1 (PD-1) pathway is associated with the regulation of T cell activation and with the apoptotic pathways of effector memory T cells. Specifically, the binding with PD-1 ligand (PD-L1) on the surface of tumor plasma cells down-regulates T cell-proliferation, thus contributing to the immune escape of tumor cells...
2018: Frontiers in Immunology
Patrick Alan Hagen, Patrick Stiff
Multiple myeloma (MM) is a malignant disorder of plasma cells primarily affecting elderly patients and is the second most commonly diagnosed hematological neoplasm. With the recent influx of effective new agents available including proteasome inhibitors, immunomodulators, targeted monoclonal antibodies, and now chimeric antigen receptor t-cell therapy (CAR-T), the treatment landscape is evolving rapidly. While the role of consolidative autologous stem cell transplantation (ASCT) in first remission is well established, in the relapsed setting following up front ASCT, the role of a second ASCT (SAT) following reinduction is less clear and understudied...
December 8, 2018: Biology of Blood and Marrow Transplantation
Homer C Adams, Frederik Stevenaert, Jakub Krejcik, Koen Van der Borght, Tina Smets, Jaime Bald, Yann Abraham, Hugo Ceulemans, Christopher Chiu, Greet Vanhoof, Saad Z Usmani, Torben Plesner, Sagar Lonial, Inger Nijhof, Henk M Lokhorst, Tuna Mutis, Niels W C J van de Donk, Amy Kate Sasser, Tineke Casneuf
Daratumumab is a CD38-targeted human monoclonal antibody with direct anti-myeloma cell mechanisms of action. Flow cytometry in relapsed and/or refractory multiple myeloma (RRMM) patients treated with daratumumab revealed cytotoxic T-cell expansion and reduction of immune-suppressive populations, suggesting immune modulation as an additional mechanism of action. Here, we performed an in-depth analysis of the effects of daratumumab on immune-cell subpopulations using high-dimensional mass cytometry. Whole-blood and bone-marrow baseline and on-treatment samples from RRMM patients who participated in daratumumab monotherapy studies (SIRIUS and GEN501) were evaluated with high-throughput immunophenotyping...
December 11, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
L Rasche, N Weinhold
BACKGROUND: Multiple myeloma (MM) is a hematologic malignancy characterized by monoclonal plasma cells infiltrating the bone marrow thereby causing anemia and lytic bone lesions. Despite significant improvement in overall survival, most MM patients inevitably, yet unpredictably, develop refractory disease and MM remains largely incurable. OBJECTIVE: This article describes the stages of progression and presents current insights into the pathogenesis of MM. MATERIAL AND METHODS: Discussion of basic conceptional works and most recent scientific publications...
December 10, 2018: Der Internist
Anne Slomp, Victor Peperzak
Apoptosis plays a key role in protection against genomic instability and maintaining tissue homeostasis, and also shapes humoral immune responses. During generation of an antibody response, multiple rounds of B-cell expansion and selection take place in germinal centers (GC) before high antigen affinity memory B-cells and long-lived plasma cells (PC) are produced. These processes are tightly regulated by the intrinsic apoptosis pathway, and malignant transformation throughout and following the GC reaction is often characterized by apoptosis resistance...
2018: Frontiers in Oncology
Alexandre Favà, Xavier Fulladosa, Nuria Montero, Juliana Draibe, Joan Torras, Montse Gomà, Josep M Cruzado
Renal injury is a common complication in multiple myeloma (MM). In fact, as many as 10% of patients with MM develop dialysis-dependent acute kidney injury related to increased free light chain (FLC) production by a plasma cell clone. Myeloma cast nephropathy (MCN) is the most prevalent pathologic diagnosis associated with renal injury, followed by light chain deposition disease and light chain amyloidosis. Several FLC removal techniques have been explored to improve kidney disease in MM but their impact on renal clinical outcomes remains unclear...
December 2018: Clinical Kidney Journal
Guy Ledergor, Assaf Weiner, Mor Zada, Shuang-Yin Wang, Yael C Cohen, Moshe E Gatt, Nimrod Snir, Hila Magen, Maya Koren-Michowitz, Katrin Herzog-Tzarfati, Hadas Keren-Shaul, Chamutal Bornstein, Ron Rotkopf, Ido Yofe, Eyal David, Venkata Yellapantula, Sigalit Kay, Moshe Salai, Dina Ben Yehuda, Arnon Nagler, Lev Shvidel, Avi Orr-Urtreger, Keren Bahar Halpern, Shalev Itzkovitz, Ola Landgren, Jesus San-Miguel, Bruno Paiva, Jonathan J Keats, Elli Papaemmanuil, Irit Avivi, Gabriel I Barbash, Amos Tanay, Ido Amit
Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors...
December 2018: Nature Medicine
Arianna Calcinotto, Arianna Brevi, Marta Chesi, Roberto Ferrarese, Laura Garcia Perez, Matteo Grioni, Shaji Kumar, Victoria M Garbitt, Meaghen E Sharik, Kimberly J Henderson, Giovanni Tonon, Michio Tomura, Yoshihiro Miwa, Enric Esplugues, Richard A Flavell, Samuel Huber, Filippo Canducci, Vincent S Rajkumar, P Leif Bergsagel, Matteo Bellone
The gut microbiota has been causally linked to cancer, yet how intestinal microbes influence progression of extramucosal tumors is poorly understood. Here we provide evidence implying that Prevotella heparinolytica promotes the differentiation of Th17 cells colonizing the gut and migrating to the bone marrow (BM) of transgenic Vk*MYC mice, where they favor progression of multiple myeloma (MM). Lack of IL-17 in Vk*MYC mice, or disturbance of their microbiome delayed MM appearance. Similarly, in smoldering MM patients, higher levels of BM IL-17 predicted faster disease progression...
December 3, 2018: Nature Communications
Tomas Jelinek, Bruno Paiva, Roman Hajek
The treatment of cancer, especially of various types of solid tumors, has been revolutionized by the blockade of the PD-1/PD-L1 pathway by immune checkpoint inhibitors. Their success amongst hematologic malignancies, however, has been limited so far to the treatment of classic Hodgkin's lymphoma, which portrays a typical overexpression of PD-1 ligands (PD-L1, PD-L2) as a consequence of changes in chromosome 9p24.1. Their current application in multiple myeloma (MM) is rather uncertain, as discordant results have been reported by distinct research groups concerning especially the expression of PD-1/PD-L1 molecules on malignant plasma cells or on the responsible immune effector cell populations, respectively...
2018: Frontiers in Immunology
Tanya M Wildes, Kenneth C Anderson
Mrs. A. is a 73-year-old woman who has developed increasing fatigue and lower back pain over the past year. The pain limits her exercise tolerance such that she can now walk only 1 block. She is a retired schoolteacher who does volunteer efforts in her community but has limited her activities due to fatigue. Karnofsky performance status is 70%. She has a history of chronic hypertension treated with a diuretic, adult-onset diabetes mellitus treated with metformin, and hypothyroidism treated with levothyroxine...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Thierry Facon, Kenneth Anderson
Mrs. A. is a 73-year-old woman who has developed increasing fatigue and lower back pain over the past year. The pain limits her exercise tolerance such that she can now walk only 1 block. She is a retired schoolteacher who does volunteer efforts in her community but has limited her activities due to fatigue. Karnofsky performance status is 70%. She has a history of chronic hypertension treated with a diuretic, adult-onset diabetes mellitus treated with metformin, and hypothyroidism treated with levothyroxine...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Maki Ohya, Koh Nakazawa, Hiroyuki Kanno
Plasma cell myeloma (PCM) is a haematological malignancy defined by aberrant proliferation of plasma cells in the bone marrow. For the diagnosis of PCM, immunostaining of light chains or surface marker analyses by flow cytometry is needed but sometimes difficult. Aberrant methylation at the carbon-5 position of cytosine results in 5-methylcytosine (5-mC), which is a well-known epigenetic hallmark of cancer in mammals. 5-mC is oxidised to 5-hydroxymethylcytosine (5-hmC), and low 5-hmC levels occur in several cancers and haematopoietic malignancies...
November 28, 2018: Pathology
Jin Shang, Zhi-Zhong Chen, Zhi-Hong Wang, Tian-Nan Wei, Wen-Bing Wu, Wei-Min Chen
OBJECTIVE: To investigate relationship of miRNA-132, miRNA-256, miRNA-143 and miRNA-145 level with antophagy and apoptosis of multiple mgeloma cells. METHODS: Human myeloma cell line U266 and normal CD138+ plasma cells were selected and used for study and detection, the 45 cases of MM were enrolled in MM group, and 40 normal persons were sellectod in control group. The expression of miRNA-132, miRNA-125b, miRNA-143 and miRNA-145 were measured by using qPCR, the expressions of autophagy-related protein (LC3-Ⅱ, LC3-Ⅰ, P62, beclin-1) and apoptosis-related molecules (cleaved-Caspase3, cleaved-Caspase7, BCL-2, BAX) were measured by using Western blot, respectively...
December 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Rasmus Sørrig, Tobias W Klausen, Morten Salomo, Annette Vangsted, Peter Gimsing
OBJECTIVES: Infections pose the greatest risk of early death in patients with Multiple Myeloma. However, few studies have analyzed the risk factors for infections in Multiple Myeloma patients. The aim of this study was to analyze the risk factors infections within a population-based MM cohort. METHODS: Using Danish registries (from 2005 to 2013), we analyzed all ICD-10 codes for infections within the first 6 months of Multiple Myeloma diagnosis in 2557 patients...
October 29, 2018: European Journal of Haematology
Ilya Noginskiy, Abraham Samra, Kendra Nielsen, Madhumati R Kalavar
Multiple myeloma (MM), a plasma cell neoplasm, has a typical presenting pattern consisting of bone pain, renal failure, anemia, and/or hypercalcemia. Even though MM is a cancer that impairs the immune system, rarely is a systemic infection the first sign of disease. In this case report, our patient presented with altered mental status due to meningitis and was later diagnosed with MM. Furthermore, we display a case of a rare but emerging and serious fungus, Candida auris , that the patient developed during his inpatient stay...
September 2018: Case Reports in Oncology
Robyn N Parks, Christopher J Kim, Zain A Al-Safi, Abigail A Armstrong, Temeka Zore, Neda A Moatamed
Chronic endometritis is characterized by plasma cell (PC) infiltration of endometrial stroma. Identification of PCs can be challenging by routine hematoxylin and eosin (H&E) stain due to the low numbers of PCs or to their being obscured by other cells in the stroma. CD138 is widely used as an ancillary immunohistochemistry stain to identify PCs; however, it has a high background reaction. In this study, multiple myeloma 1 (MUM1) transcription factor is introduced as an alternative PC marker in endometrial tissues...
November 28, 2018: International Journal of Surgical Pathology
Nathan G Dolloff
Immunoglobulin heavy chain (IgH) translocations are common and early oncogenic events in B cell and plasma cell malignancies including B cell non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). IgH translocations bring oncogenes into close proximity with potent enhancer elements within the IgH locus, leading to oncogene up-regulation. As IgH enhancer activity is tightly controlled by B cell lineage-specific signaling and transcriptional networks, we hypothesized that IgH enhancers are potentially druggable targets/elements...
November 27, 2018: Cancer Biology & Therapy
Justin R Arnall, Saad Z Usmani, Hawawu Adamu, Joseph Mishkin, Manisha Bhutani
Systemic light-chain (AL) amyloidosis is a rare hematologic disorder where proteins infiltrate tissues leading to organ failure and death. Cardiac involvement, present in ∼70% of patients, determines stage and prognosis of the disease, with advanced involvement having a median survival of six months. The treatment of light-chain amyloidosis is directed at recovering organ function with therapeutic strategies following those of multiple myeloma with plasma cell-directed therapies. The use of single agent daratumumab has been reported in light-chain amyloidosis achieving rapid and deep responses...
November 26, 2018: Journal of Oncology Pharmacy Practice
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