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https://www.readbyqxmd.com/read/28099581/minimal-residual-disease-detection-in-tunisian-b-acute-lymphoblastic-leukemia-based-on-immunoglobulin-gene-rearrangements
#1
S Besbes, W S Hamadou, M L Boulland, Y B Youssef, B Achour, H Regaieg, A Khelif, T Fest, Z Soua
IGH gene rearrangement and IGK-Kde gene deletion can be used as molecular markers for the assessment of B lineage acute lymphoblastic leukemia (B-ALL). Minimal residual disease detected based on those markers is currently the most reliable prognosis factor in B-ALL. The aim of this study was to use clonal IGH/IGK-Kde gene rearrangements to confirm B-ALL diagnosis and to evaluate the treatment outcome of Tunisian leukemic patients by monitoring the minimal residual disease (MRD) after induction chemotherapy...
January 16, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28088785/the-igh-locus-3-cis-regulatory-super-enhancer-co-opts-aid-for-allelic-transvection
#2
Sandrine Le Noir, Brice Laffleur, Claire Carrion, Armand Garot, Sandrine Lecardeur, Eric Pinaud, Yves Denizot, Jane Skok, Michel Cogné
Immunoglobulin heavy chain (IgH) alleles have ambivalent relationships: they feature both allelic exclusion, ensuring monoallelic expression of a single immunoglobulin (Ig) allele, and frequent inter-allelic class-switch recombination (CSR) reassembling genes from both alleles. The IgH locus 3' regulatory region (3'RR) includes several transcriptional cis-enhancers promoting activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (SHM) and CSR, and altogether behaves as a strong super-enhancer...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28069803/ig-light-chain-precedes-heavy-chain-gene-rearrangement-during-development-of-b-cells-in-swine
#3
Marek Sinkora, Jana Sinkorova, Katerina Stepanova
The current mammalian paradigm states that 1) rearrangements in the IgH locus precede those in IgL loci, 2) IgLλ genes rearrange only when IgLκ genes are consumed, and 3) the surrogate L chain is necessary for selection of productive IgH gene rearrangements. We show in swine that IgL rearrangements precede IgH gene rearrangements, resulting in the expression of naked IgL on a surface of precursor B cells. Findings also suggest that there is no dependency on the surrogate L chain, and thus the authentic IgL proteins may be used for selection of the IgH repertoire...
January 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28041846/change-in-ighv-mutational-status-of-cll-suggests-origin-from-multiple-clones
#4
Afaf Osman, Christopher D Gocke, Douglas E Gladstone
BACKGROUND: Fluorescence in situ hybridization and immunoglobulin (Ig) heavy-chain variable-region (IgHV) mutational status are used to predict outcome in chronic lymphocytic leukemia (CLL). Although DNA aberrations change over time, IgHV sequences and mutational status are considered stable. PATIENTS AND METHODS: In a retrospective review, 409 CLL patients, between 2008 and 2015, had IgHV analysis: 56 patients had multiple analyses performed. Seven patients' IgHV results changed: 2 from unmutated to mutated and 5 from mutated to unmutated IgHV sequence...
November 21, 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28039078/molecular-monitoring-after-autologous-stem-cell-transplantation-and-preemptive-rituximab-treatment-of-molecular-relapse-results-from-the-nordic-mantle-cell-lymphoma-studies-mcl2-and-mcl3-with-median-follow-up-of-8-5-years
#5
Arne Kolstad, Lone Bredo Pedersen, Christian W Eskelund, Simon Husby, Kirsten Grønbæk, Mats Jerkeman, Anna Laurell, Riikka Räty, Erkki Elonen, Niels Smedegaard Andersen, Peter deNully Brown, Eva Kimby, Hans Bentzen, Christer Sundström, Mats Ehinger, Marja-Liisa Karjalainen-Lindsberg, Jan Delabie, Elisabeth Ralfkiær, Unn-Merete Fagerli, Herman Nilsson-Ehle, Grete Fossum Lauritzsen, Outi Kuittinen, Carsten Niemann, Christian Hartman Geisler
The main objectives of the present study were to monitor minimal residual disease (MRD) in the bone marrow of patients with mantle cell lymphoma (MCL) to predict clinical relapse and guide preemptive treatment with rituximab. Among the patients enrolled in 2 prospective trials by the Nordic Lymphoma Group, 183 who had completed autologous stem cell transplantation (ASCT) and in whom an MRD marker had been obtained were included in the our analysis. Fresh samples of bone marrow were analyzed for MRD by a combined standard nested and quantitative real-time PCR assay for Bcl-1/immunoglobulin heavy chain gene (IgH) and clonal IgH rearrangements...
December 27, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28038713/expression-of-lef1-in-mantle-cell-lymphoma
#6
Dennis P O'Malley, John P Lee, Andrew M Bellizzi
Small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL/SLL) and mantle cell lymphoma (MCL) usually are distinctly different in regard to clinical presentation, morphology, immunophenotype and molecular/genetic findings. In spite of this, select cases may show overlapping characteristics and represent a diagnostic challenge. Recently LEF1 staining was identified as a fairly characteristic finding in CLL/SLL, with positivity identified in up to 95% of cases. LEF1 staining has not been reported as being present in cases of MCL, making this stain a useful tool in distinguishing these diagnoses...
February 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28038709/signet-ring-cell-lymphoma-clinicopathologic-immunohistochemical-and-fluorescence-in-situ-hybridization-studies-of-7-cases
#7
Shanxiang Zhang, Jihong Sun, Yanan Fang, Mehdi Nassiri, Lanting Liu, Jiehao Zhou, Ryan Stohler, Haki Choi, Gail H Vance
CONTEXT: Signet-ring cell lymphoma (SRCL) is a rare morphologic variant of non-Hodgkin lymphoma. Although it was initially reported as a rare morphologic variant of follicular lymphoma (FL), SRCL has to date been described in most types of non-Hodgkin lymphoma, mostly as single-case reports. OBJECTIVE: To study SRCL systematically by immunohistochemical stains and fluorescent in situ hybridization analyses. DESIGN: Seven SRCL cases were stained for CD3, CD5, CD20, PAX-5, CD10, CD21, CD23, cyclin D1, BCL2, BCL6, Ki-67, and MUM-1, and were analyzed by fluorescent in situ hybridization for BCL2, BCL6, MYC, and MALT1 rearrangements...
February 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28038705/cyclin-d1-expression-and-polysomy-in-lymphocyte-predominant-cells-of-nodular-lymphocyte-predominant-hodgkin-lymphoma
#8
Benjamin B Cho, Sarah M Kelting, Alejandro A Gru, Robin D LeGallo, Patcharin Pramoonjago, Teresa A Goldin, Christopher T Heitz, Nadine S Aguilera
Cyclin D1 protein expression in lymphocytes is classically associated with mantle cell lymphoma. Although increasingly recognized in other lymphoproliferative disorders, cyclin D1 expression and CCND1 gene abnormalities have not been well studied in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Using a double stain for CD20/cyclin D1, we quantified cyclin D1 expression in 10 cases of NLPHL and correlated those findings with SOX11 expression, CCND1 gene abnormalities, and clinical data. For comparison, we examined 5 cases of T cell-/histiocyte-rich large B-cell lymphoma (THRLBCL)...
February 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28033648/characterisation-of-the-genomic-landscape-of-crlf2-rearranged-acute-lymphoblastic-leukemia
#9
Lisa J Russell, Lisa Jones, Amir Enshaei, Stefano Tonin, Sarra L Ryan, Jeyanthy Eswaran, Sirintra Nakjang, Elli Papaemmanuil, Jose M C Tubio, Adele K Fielding, Ajay Vora, Peter J Campbell, Anthony V Moorman, Christine J Harrison
Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5-15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We aimed to determine the clinical and genetic landscape of those with IGH-CRLF2 or P2RY8-CRLF2 (CRLF2-r) using multiple genomic approaches. Clinical and demographic features of CRLF2-r patients were characteristic of B-ALL. Patients with IGH-CRLF2 were older (14 y vs. 4 y, P < .001), while the incidence of CRLF2-r among Down syndrome patients was high (50/161, 31%)...
December 29, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28032914/pleomorphic-mantle-cell-lymphoma-morphologically-mimicking-diffuse-large-b-cell-lymphoma-common-cyclin-d1-negativity-and-a-simple-immunohistochemical-algorithm-to-avoid-the-diagnostic-pitfall
#10
Wen-Yu Chuang, Hung Chang, Gwo-Jyh Chang, Tzu-Hao Wang, Yu-Sun Chang, Tong-Hong Wang, Chi-Ju Yeh, Shir-Hwa Ueng, Hui-Ping Chien, Chiu-Yueh Chang, Yung-Liang Wan, Chuen Hsueh
AIMS: To characterize the clinicopathologic and genetic features of pleomorphic mantle cell lymphoma (PMCL) which morphologically mimics diffuse large B-cell lymphoma (DLBCL). METHODS AND RESULTS: We systematically screened 500 B-cell lymphomas morphologically compatible with DLBCL using an immunohistochemical algorithm of three markers (CD5, cyclin D1 and SOX11). Ten cases of PMCL were identified for further study, and surprisingly four (40%) of them were cyclin D1-negative...
December 29, 2016: Histopathology
https://www.readbyqxmd.com/read/28028120/ccnd1-igh-fusion-amplification-and-myc-copy-number-gain-in-a-case-of-pleomorphic-variant-mantle-cell-lymphoma
#11
Yuan Miao, Pei Lin, Wei Wang, L Jeffrey Medeiros, Xinyan Lu
OBJECTIVES: Mantle cell lymphoma (MCL) may present de novo or undergo progression to a clinically aggressive variant, known as a blastoid or pleomorphic variant. We report an unusual case of classic MCL in a 78-year-old man with a typical immunophenotype, including CD5 positivity, who subsequently relapsed with CD5-negative pleomorphic variant MCL. METHODS: Biopsy specimens were evaluated using Wright-Giemsa-stained or H&E-stained sections, flow cytometry, immunohistochemistry, conventional cytogenetic, next-generation sequencing, and fluorescence in situ hybridization...
December 27, 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28011932/immunodominance-of-antibody-recognition-of-the-hiv-envelope-v2-region-in-ig-humanized-mice
#12
Kevin Wiehe, Nathan I Nicely, Bradley Lockwood, Masayuki Kuraoka, Kara Anasti, Sabrina Arora, Cindy M Bowman, Christina Stolarchuk, Robert Parks, Krissey E Lloyd, Shi-Mao Xia, Ryan Duffy, Xiaoying Shen, Christos A Kyratsous, Lynn E Macdonald, Andrew J Murphy, Richard M Scearce, M Anthony Moody, S Munir Alam, Laurent Verkoczy, Georgia D Tomaras, Garnett Kelsoe, Barton F Haynes
In the RV144 gp120 HIV vaccine trial, decreased transmission risk was correlated with Abs that reacted with a linear epitope at a lysine residue at position 169 (K169) in the HIV-1 envelope (Env) V2 region. The K169 V2 response was restricted to Abs bearing Vλ rearrangements that expressed aspartic acid/glutamic acid in CDR L2. The AE.A244 gp120 in AIDSVAX B/E also bound to the unmutated ancestor of a V2-glycan broadly neutralizing Ab, but this Ab type was not induced in the RV144 trial. In this study, we sought to determine whether immunodominance of the V2 linear epitope could be overcome in the absence of human Vλ rearrangements...
December 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27998928/the-cell-cycle-restricts-activation-induced-cytidine-deaminase-activity-to-early-g1
#13
Qiao Wang, Kyong-Rim Kieffer-Kwon, Thiago Y Oliveira, Christian T Mayer, Kaihui Yao, Joy Pai, Zhen Cao, Marei Dose, Rafael Casellas, Mila Jankovic, Michel C Nussenzweig, Davide F Robbiani
Activation-induced cytidine deaminase (AID) converts cytosine into uracil to initiate somatic hypermutation (SHM) and class switch recombination (CSR) of antibody genes. In addition, this enzyme produces DNA lesions at off-target sites that lead to mutations and chromosome translocations. However, AID is mostly cytoplasmic, and how and exactly when it accesses nuclear DNA remains enigmatic. Here, we show that AID is transiently in spatial contact with genomic DNA from the time the nuclear membrane breaks down in prometaphase until early G1, when it is actively exported into the cytoplasm...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27995603/role-of-gamma-interferon-and-inflammatory-monocytes-in-driving-colonic-inflammation-during-acute-c-difficile-infection-in-mice
#14
Andrew J McDermott, Nicole R Falkowski, Roderick A McDonald, Charles R Frank, Chinmay R Pandit, Vincent B Young, Gary B Huffnagle
The inflammatory response to the colonic pathogen Clostridium difficile is characterized by the induction of inflammatory cytokines including Interleukin-23 (IL-23) and interferon gamma (IFNγ) and the recruitment of myeloid cells including Ly6C(H)(igh) monocytes. IL-23KO mice showed reduced expression of the monocyte chemokines Ccl4 and Ccl7, but not Ccl2, as well as reduced Ly6C(H)(igh) Ly6G(M)(id) monocyte recruitment to the colon in response to C. difficile colitis. C. difficile-infected CCR2(-/-) (CCR2KO) mice showed a significant defect in Ly6C(H)(igh) Ly6G(M)(id) monocyte recruitment to the colon in response to C...
December 20, 2016: Immunology
https://www.readbyqxmd.com/read/27988336/jsi-124-inhibits-ige-production-in-an-ige-b-cell-line
#15
Lulu Cui, Jiacheng Bi, Dehong Yan, Xiufeng Ye, Mingxing Zheng, Guang Yu, Xiaochun Wan
IgE is a key effector molecule in atopic diseases; however, the regulation mechanisms of IgE production in IgE B cells remain poorly understood. In the present study, we demonstrate that JSI-124 (cucurbitacin I), a selective STAT3 inhibitor, selectively inhibits production of IgE by a human IgE B cell line, CRL-8033 cells, while does not affect the IgG production by IgG B cell lines. In the aspect of molecular mechanism, we found that Igλ, but not Ighe, gene expression was suppressed by JSI-124. The above effects of JSI-124 were not mediated by affecting cellular proliferation or apoptosis...
December 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27974207/dna-replication-origins-in-immunoglobulin-switch-regions-regulate-class-switch-recombination-in-an-r-loop-dependent-manner
#16
Eva-Maria Wiedemann, Mihaela Peycheva, Rushad Pavri
Class switch recombination (CSR) at the immunoglobulin heavy chain (IgH) locus generates antibody isotypes. CSR depends on double-strand breaks (DSBs) induced by activation-induced cytidine deaminase (AID). Although DSB formation and repair machineries are active in G1 phase, efficient CSR is dependent on cell proliferation and S phase entry; however, the underlying mechanisms are obscure. Here, we show that efficient CSR requires the replicative helicase, the Mcm complex. Mcm proteins are enriched at IgH switch regions during CSR, leading to assembly of facultative replication origins that require Mcm helicase function for productive CSR...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27942583/tissue-distribution-and-clonal-diversity-of-the-t-and-b-cell-repertoire-in-type-1-diabetes
#17
Howard R Seay, Erik Yusko, Stephanie J Rothweiler, Lin Zhang, Amanda L Posgai, Martha Campbell-Thompson, Marissa Vignali, Ryan O Emerson, John S Kaddis, Dave Ko, Maki Nakayama, Mia J Smith, John C Cambier, Alberto Pugliese, Mark A Atkinson, Harlan S Robins, Todd M Brusko
The adaptive immune repertoire plays a critical role in type 1 diabetes (T1D) pathogenesis. However, efforts to characterize B cell and T cell receptor (TCR) profiles in T1D subjects have been largely limited to peripheral blood sampling and restricted to known antigens. To address this, we collected pancreatic draining lymph nodes (pLN), "irrelevant" nonpancreatic draining lymph nodes, peripheral blood mononuclear cells (PBMC), and splenocytes from T1D subjects (n = 18) and control donors (n = 9) as well as pancreatic islets from 1 T1D patient; from these tissues, we collected purified CD4(+) conventional T cells (Tconv), CD4(+) Treg, CD8(+) T cells, and B cells...
December 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27930376/excimer-light-treatment-for-idiopathic-guttate-hypomelanosis-a-pilot-study
#18
Jennifer R S Gordon, Kellie E Reed, Katherine R Sebastian, Ammar M Ahmed
BACKGROUND: Idiopathic guttate hypomelanosis (IGH) is a commonly acquired benign leukoderma characterized by multiple discrete, hypo- or depigmented macules often on extremities that can be aesthetically undesirable for patients. This is the first study using excimer laser for treatment. OBJECTIVE: To determine the effectiveness of excimer laser for repigmentation of idiopathic guttate hypomelanosis. METHODS AND MATERIALS: In this longitudinal, split-body controlled, single-blinded pilot study, 6 patients were treated with excimer laser for 12 weeks using the vitiligo protocol...
December 2, 2016: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/27925177/t-cell-diversification-reflects-antigen-selection-in-the-blood-of-patients-on-immune-checkpoint-inhibition-and-may-be-exploited-as-liquid-biopsy-biomarker
#19
Nuray Akyüz, Anna Brandt, Alexander Stein, Simon Schliffke, Thorben Mährle, Julia Quidde, Eray Goekkurt, Sonja Loges, Thomas Haalck, Christopher Ford, Anne Marie Asemissen, Benjamin Thiele, Janina Radloff, Toni Thenhausen, Artus Krohn-Grimberghe, Carsten Bokemeyer, Mascha Binder
Cancer immunotherapy with antibodies targeting immune checkpoints, such as programmed cell death protein 1 (PD-1), shows encouraging results, but reliable biomarkers predicting response to this costly and potentially toxic treatment approach are still lacking. To explore an immune signature predictive for response, we performed liquid biopsy immunoprofiling in 18 cancer patients undergoing PD-1 inhibition before and shortly after initiation of treatment by multicolor flow cytometry and next-generation T- and B-cell immunosequencing (TCRß/IGH)...
December 7, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27907150/molecular-characterization-of-two-monoclonal-antibodies-against-the-same-epitope-on-b-cell-receptor-associated-protein-31
#20
Won-Tae Kim, Saemina Shin, Hyo Jeong Hwang, Min Kyu Kim, Han-Sung Jung, Hwangseo Park, Chun Jeih Ryu
Previously, we showed that B-cell receptor associated protein 31 (BAP31), an endoplasmic reticulum (ER) membrane chaperone, is also expressed on the cell surface by two monoclonal antibodies (MAbs) 297-D4 and 144-A8. Both MAbs recognize the same linear epitope on the C-terminal domain of BAP31, although they were independently established. Here, flow cytometric analysis showed that 144-A8 had additional binding properties to some cells, as compared to 297-D4. Quantitative antigen binding assays also showed that 144-A8 had higher antigen binding capacity than 297-D4...
2016: PloS One
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