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Nour Ghazzaui, Alexis Saintamand, Hussein Issaoui, Christelle Vincent-Fabert, Yves Denizot
Deregulation and mutations of c-myc have been reported in multiple mature B-cell malignancies such as Burkitt lymphoma, myeloma and plasma cell lymphoma. After translocation into the immunoglobulin heavy chain (IgH) locus, c-myc is constitutively expressed under the control of active IgH cis-regulatory enhancers. Those located in the IgH 3' regulatory region (3'RR) are master control elements of transcription. Over the past decade numerous convincing demonstrations of 3'RR's contribution to mature c-myc-induced lymphomagenesis have been made using transgenic models with various types of IgH-c-myc translocations and transgenes...
October 8, 2016: Oncotarget
Steven R Wiley, Vanitha S Raman
Adjuvants in vaccine formulations are designed to enhance immune responses against a target antigen or pathogen. The ability of these vaccines to induce activation and differentiation of mature naïve B cells to produce pathogen-specific antibodies (immunoglobulins; Ig) helps guarantee long-lived humoral immunity. This process involves clonal expansion of antigen-specific B cells, genomic rearrangement of Ig heavy (IgH) and light (IgL) loci, somatic hypermutation (SHM), and clonal selection for affinity-matured antibody, resulting in a vast but directed repertoire of B cells expressing highly specific antibody proteins...
2017: Methods in Molecular Biology
Koji Komatsu, Tsutomu Sakai, Toshikatsu Kaburaki, Hideki Tsuji, Hiroshi Tsuneoka
BACKGROUND: In 2014, Pang et al. reported three cases with vitelliform submaculopathy as a preceding lesion of primary intraocular lymphoma (PIOL). Here, we report a case with an atypical presentation of PIOL who initially presented with vitelliform submaculopathy, vitreous haze and preripheral retinal focus. CASE PRESENTATION: A 73-year-old female initially visited another hospital with a chief complaint of acute reduced vision in the right eye. Funduscopic examination of the right eye showed a yellowish retinal lesion at the fovea with vitreous haze and retinal foci scattered in the peripheral region...
October 3, 2016: BMC Ophthalmology
Michel Varrin-Doyer, Kara L Pekarek, Collin M Spencer, Claude C A Bernard, Raymond A Sobel, Bruce A C Cree, Ulf Schulze-Topphoff, Scott S Zamvil
OBJECTIVE: To evaluate the influence of oral laquinimod, a candidate multiple sclerosis (MS) treatment, on induction of T follicular helper cells, development of meningeal B cell aggregates, and clinical disease in a spontaneous B cell-dependent MS model. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by immunization with recombinant myelin oligodendrocyte glycoprotein (rMOG) protein. Spontaneous EAE was evaluated in C57BL/6 MOG p35-55-specific T cell receptor transgenic (2D2) × MOG-specific immunoglobulin (Ig)H-chain knock-in (IgH(MOG-ki) [Th]) mice...
October 2016: Neurology® Neuroimmunology & Neuroinflammation
M Mortamais, J A Ash, J Harrison, J Kaye, J Kramer, C Randolph, C Pose, B Albala, M Ropacki, C W Ritchie, K Ritchie
Significant progress has been made in characterizing the biological changes occurring in preclinical Alzheimer's disease (AD). Cognitive dysfunction has been viewed, however, as a late-stage phenomenon, despite increasing evidence that changes may be detected in the decades preceding dementia. In the absence of comprehensive evidence-based guidelines for preclinical cognitive assessment, longitudinal cohort and neuroimaging studies have been reviewed to determine the temporal order and brain biomarker correlates of specific cognitive functions...
October 1, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Sandhya R Pulivarthy, Mattia Lion, Guray Kuzu, Adam G W Matthews, Mark L Borowsky, John Morris, Robert E Kingston, Jonathan H Dennis, Michael Y Tolstorukov, Marjorie A Oettinger
We show that the physical distribution of nucleosomes at antigen receptor loci is subject to regulated cell type-specific and lineage-specific positioning and correlates with the accessibility of these gene segments to recombination. At the Ig heavy chain locus (IgH), a nucleosome in pro-B cells is generally positioned over each IgH variable (VH) coding segment, directly adjacent to the recombination signal sequence (RSS), placing the RSS in a position accessible to the recombination activating gene (RAG) recombinase...
October 3, 2016: Proceedings of the National Academy of Sciences of the United States of America
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
Kenji Nishida, Yuka Sogabe, Ayako Makihara, Akemi Senoo, Hisanori Morimoto, Mai Takeuchi, Yuka Gion, Tadashi Yoshino, Yasuharu Sato
A 41-year-old man was diagnosed with immunoglobulin G4-related disease (IgG4-RD) in both eyelids 4 years ago and exhibited good response to steroid therapy. However, rapid swelling of the right eyelid lesion was recently observed. As IgG4-RD progression was suspected, biopsy was performed. Although the histology was consistent with IgG4-RD, the infiltrating large atypical lymphoid cells showed immunoglobulin light-chain restriction and IgH gene rearrangement. Consequently, he was diagnosed with extranodal marginal zone lymphoma with abundant IgG4-positive cells...
August 11, 2016: Modern Rheumatology
Magdalena B Rother, Kristin Jensen, Mirjam van der Burg, Fleur S van de Bovenkamp, Roel Kroek, Wilfred F J van IJcken, Vincent H J van der Velden, Tom Cupedo, Ole K Olstad, Jacques J M van Dongen, Menno C van Zelm
Newborns are unable to mount antibody responses towards certain antigens. This has been related to the restricted repertoire of immunoglobulin (Ig) genes of their B cells. The mechanisms underlying the restricted fetal Ig gene repertoire are currently unresolved. We here addressed this with detailed molecular and cellular analysis of human precursor-B cells from fetal liver, fetal bone marrow (BM), and pediatric BM. In the absence of selection processes, fetal B-cell progenitors more frequently used proximal V, D and J genes in complete IGH gene rearrangements, despite normal Ig locus contraction...
2016: Scientific Reports
R Cianci, S Lolli, D Pagliari, G Gambassi, S Frosali, R Marmo, G Melioli, A Orlando, E E Newton, E Serone, R Landolfi, F Pandolfi, D Frezza
OBJECTIVE: To study the 3' immunoglobulin heavy-chain regulatory region (3'RR) enhancer complex, active in class switching recombination and in B-cells, in Crohn's disease. PATIENTS AND METHODS: A total of 167 patients [79 females (47.3%) and 88 males (52.7%)] affected by Crohn's disease were enrolled in the study. As a control, we included 64 healthy subjects, age and sex matched, from the same geographical area. Blood tests were performed on all subjects to determine their antibody levels and to detect the presence of any possible infections...
September 2016: European Review for Medical and Pharmacological Sciences
Sawsen Besbes, Walid-Sabri Hamadou, Marie-Laure Boulland, Marie-Paule Lefranc, Yosra Ben Youssef, Béchir Achour, Abderrahim Khelif, Thierry Fest, Zohra Soua
INTRODUCTION: The monitoring of minimal residual disease (MRD) approach in patients diagnosed with B-acute lymphoblastic leukemia (B-ALL) allows an early detection of residual clones inducing relapses and therefore appropriate therapy strategy. The molecular markers may identify and quantify the residual blasts in B-ALL with normal cytology. In this study, we aimed to use combined IKZF1, IGH and IGK immunoglobulin genes for diagnosis and MRD monitoring in B-ALL sample using MLPA, multiplex PCR and real-time quantitative PCR...
September 7, 2016: Bulletin du Cancer
Ana E Suárez, M J Artiga, Carlos Santonja, Santiago Montes-Moreno, P De Pablo, Luis Requena, Miguel A Piris, Socorro M Rodríguez-Pinilla
Plasma cell proliferations in specific cutaneous lesions of angioimmunoblastic T-cell lymphoma(AITL) are very uncommon. Here, we report a case of clonal plasma cell proliferation in skin with heavy-chain-immunoglobulin-isotype-switch after cutaneous disease progression. Histopathologically, initial plaque lesions were suggestive of marginal-zone B-cell-lymphoma. Nevertheless, this 77-year-old lady was diagnosed with AITL after the progression of skin lesions from plaques to nodular tumors. A lymph node biopsy confirmed the diagnosis...
September 6, 2016: Journal of Cutaneous Pathology
Pengfei Cao, Guiyuan Li, Qian Tan, Ying Zhang, Guoping Zhang, Xiaolin Li, Yuxiang He
OBJECTIVE: To investigate several abnormal genes by the fluorescence in situ hybridization (FISH) in multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS) and reactive plasmacytosis (RP), and to increase the diagnosis and differential diagnosis levels for these common plasma diseases. 
 METHODS: The clinical manifestations, image and laboratory tests and the FISH detection were retrospectively analyzed in 61 cases of newly diagnosed MM, 20 cases of MGUS and 20 cases of RP from August, 2012 to February, 2015 in the Xiangya Hospital of Central South University...
July 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
N Bolli, Y Li, V Sathiaseelan, K Raine, D Jones, P Ganly, F Cocito, G Bignell, M A Chapman, A S Sperling, K C Anderson, H Avet-Loiseau, S Minvielle, P J Campbell, N C Munshi
Genomic lesions are not investigated during routine diagnostic workup for multiple myeloma (MM). Cytogenetic studies are performed to assess prognosis but with limited impact on therapeutic decisions. Recently, several recurrently mutated genes have been described, but their clinical value remains to be defined. Therefore, clinical-grade strategies to investigate the genomic landscape of myeloma samples are needed to integrate new and old prognostic markers. We developed a target-enrichment strategy followed by next-generation sequencing (NGS) to streamline simultaneous analysis of gene mutations, copy number changes and immunoglobulin heavy chain (IGH) translocations in MM in a high-throughput manner, and validated it in a panel of cell lines...
2016: Blood Cancer Journal
Peter M Lee, Ken Siangchin, Sophie Song, David Shabsovich, Yalda Naeini, Carlos A Tirado
The t(11;14)(q13;q32) involving IGH and CCND1 a nd t(9;22) (q34;q11.2) involving BCR and ABL1 are common abnormalities in plasma cell myeloma (PCM) and chronic myelogenous leukemia (CML), respectively. However, the concurrence of the two malignancies is extremely rare. Herein, we present a case of an 87-year-old male who presented with anemia and monocytosis. FISH studies on a bone marrow sample enriched for plasma cells detected a t(11;14) positive for IGH and CCND1 fusion in 92% of nuclei. However, cytogenetic analysis of the bone marrow revealed a t(9;22)(q34;q11...
2016: Journal of the Association of Genetic Technologists
Qiang Zhuang, Lina Xiang, Hanyan Xu, Fang Fang, Chongyun Xing, Bin Liang, Kang Yu, Jianhua Feng
We retrospectively analyzed the association between mean platelet volume (MPV) and prognosis in 62 newly diagnosed multiple myeloma (MM) patients. The associations between MPV and clinical characteristics were assessed. The log-rank test and the Cox proportional hazards model were used to evaluate the effect of MPV on survival. A MPV value of 8.50 fl was considered to be the optimal cut-off value for prognosis. MPV was associated with IgA isotype (P=0.012), serum creatinine concentration > 176.8 μmol/L (P=0...
August 23, 2016: Oncotarget
Anthony B Eason, Sang-Hoon Sin, Carolina Lin, Blossom Damania, Steven Park, Yuri Fedoriw, Carlos E Bacchi, Dirk P Dittmer
Endemic Burkitt lymphoma (eBL) is primarily a childhood cancer in parts of Africa and Brazil. Classic studies describe eBL as a homogeneous entity based on t(8;14) IgH-Myc translocation and clinical response to cytotoxic therapy. By contrast, sporadic BL (sBL) in Western countries is considered more heterogeneous, and affects both children and adults. It is overrepresented in AIDS patients. Unlike diffuse large B cell lymphoma (DLBCL), molecular subtypes within BL have not been well defined. We find that differential IgM positivity can be used to describe two subtypes of pediatric Burkitt lymphoma both in a high incidence region (Brazil), as well as in a sporadic region (US), suggesting the phenotype is not necessarily geographically isolated...
August 23, 2016: Oncotarget
Tobias Herold, Stephanie Schneider, Klaus Metzeler, Martin Neumann, Luise Hartmann, Kathryn G Roberts, Nikola P Konstandin, Philipp A Greif, Kathrin Bräundl, Bianka Ksienzyk, Natalia Huk, Irene Schneider, Evelyn Zellmeier, Vindi Jurinovic, Ulrich Mansmann, Wolfgang Hiddemann, Charles G Mullighan, Stefan K Bohlander, Karsten Spiekermann, Dieter Hölzer, Monika Brüggemann, Claudia D Baldus, Martin Dreyling, Nicola Gökbuget
Philadelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was the genetic and clinical characterization of Ph-like ALL in adults. Twenty-six (13%) of 207 adult B-cell precursor ALL (BCP-ALL) patients (median age: 42 years) were classified as Ph-like using gene expression profiling. The frequency of Ph-like ALL was 27% among 95 BCP-ALL patients negative for BCR-ABL1 and MLL rearrangements...
August 25, 2016: Haematologica
Anna Lucia Peluso, Antonio Ieni, Chiara Mignogna, Pio Zeppa
Lymph node (LN) fine-needle cytology (FNC) coupled with flow cytometry immunophenotyping provides relevant information for the diagnosis of non-Hodgkin lymphoma (NHL). Numerous studies have shown FNC samples to be suitable for different molecular procedures; in this review, some of the molecular procedures most commonly employed for NHL are briefly described and evaluated in this perspective. Fluorescence in situ hybridization and chromogenic in situ hybridization are briefly described. Polymerase chain reaction (PCR)-based assays are used to identify and quantify mutations and translocations, namely immunoglobulin (IGH) and T-cell receptor rearrangements by clonality testing and IGVH somatic hypermutations either by Sanger sequencing, single-strand conformational polymorphisms or RT-PCR strategies...
2016: Acta Cytologica
Ahrom Kim, Li Han, Gabriel E Santiago, Ramiro E Verdun, Kefei Yu
The ∼28-kb 3' regulatory region (3'RR), which is located at the most distal 3' region of the Ig H chain locus, has multiple regulatory functions that control IgH expression, class-switch recombination (CSR), and somatic hypermutation. In this article, we report that deletion of the entire 3'RR in a mouse B cell line that is capable of robust cytokine-dependent CSR to IgA results in reduced, but not abolished, CSR. These data suggest that 3'RR is not absolutely required for CSR and, thus, is not essential for targeting activation-induced cytidine deaminase to S regions, as was suggested...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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