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https://www.readbyqxmd.com/read/28646116/tonic-b-cell-receptor-signaling-in-diffuse-large-b-cell-lymphoma
#1
Ondrej Havranek, Jingda Xu, Stefan Köhrer, Zhiqiang Wang, Lisa Becker, Justin M Comer, Jared Henderson, Wencai Ma, John Man Chun Ma, Jason R Westin, Dipanjan Ghosh, Nicholas Shinners, Luhong Sun, Allen F Yi, Anusha R Karri, Jan A Burger, Tomasz Zal, R Eric Davis
We used CRISPR/Cas9-mediated genomic modification to investigate B-cell receptor (BCR) signaling in cell lines of diffuse large B-cell lymphoma (DLBCL). Three manipulations that altered BCR genes without affecting surface BCR levels showed that BCR signaling differs between the germinal center B-cell (GCB) subtype, which is insensitive to BTK inhibition by ibrutinib, and the activated B-cell (ABC) subtype. Replacing antigen-binding BCR regions had no effect on BCR signaling in GCB-DLBCL lines, reflecting this subtype's exclusive use of tonic BCR signaling...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28644138/comparative-analysis-of-primary-versus-relapse-refractory-dlbcl-identifies-shifts-in-mutation-spectrum
#2
Danielle M Greenawalt, Winnie S Liang, Sakina Saif, Justin Johnson, Petar Todorov, Austin Dulak, Daniel Enriquez, Rebecca Halperin, Ambar Ahmed, Vladislav Saveliev, John Carpten, David Craig, J Carl Barrett, Brian Dougherty, Michael Zinda, Stephen Fawell, Jonathan R Dry, Kate Byth
Current understanding of the mutation spectrum of relapsed/refractory (RR) tumors is limited. We performed whole exome sequencing (WES) on 47 diffuse large B cell lymphoma (DLBCL) tumors that persisted after R-CHOP treatment, 8 matched to primary biopsies. We compared genomic alterations from the RR cohort against two treatment-naïve DLBCL cohorts (n=112). While the overall number and types of mutations did not differ significantly, we identified frequency changes in DLBCL driver genes. The overall frequency of MYD88 mutant samples increased (12% to 19%), but we noted a decrease in p...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643426/cell-of-origin-classification-by-gene-expression-and-myc-rearrangements-in-diffuse-large-b-cell-lymphoma-of-children-and-adolescents
#3
Monika Szczepanowski, Jonas Lange, Christian W Kohler, Neus Masque-Soler, Martin Zimmermann, Sietse M Aukema, Michael Altenbuchinger, Thorsten Rehberg, Friederike Mahn, Reiner Siebert, Rainer Spang, Birgit Burkhardt, Wolfram Klapper
We present the largest series of diffuse large B-cell lymphoma (DLBCL) in patients younger than 18 years analysed to date by gene expression profiling using Nanostring technology to identify molecular subtypes and fluorescent in situ hybridization for translocations of MYC. We show that the activated B cell-like subtype of DLBCL is exceedingly rare in children and - in contrast to adults- not associated with outcome. Furthermore, we review the current literature and demonstrate that MYC translocations are not more frequent in paediatric compared to adult DLBCL...
June 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28643323/favourable-outcomes-of-poor-prognosis-diffuse-large-b-cell-lymphoma-patients-treated-with-dose-dense-rituximab-high-dose-methotrexate-and-six-cycles-of-chop-14-compared-to-first-line-autologous-transplantation
#4
Tim Strüßmann, Kristina Fritsch, Axel Baumgarten, Thomas Fietz, Monika Engelhardt, Roland Mertelsmann, Gabriele Ihorst, Justus Duyster, Jürgen Finke, Reinhard Marks
The optimal therapeutic approach for young diffuse large B-cell lymphoma (DLBCL) patients with high-intermediate and high-risk age-adjusted international prognostic index (aaIPI) remains unknown. Hereby we report a 10-year single-centre study of 63 consecutively treated patients. To optimize outcome, two approaches were carried out: Cohort 1 patients received four cycles R-CHOP-21 (rituximab, cyclophosphamide, daunorubicin, vincristine, prednisolone over 21 days) followed by first-line high-dose chemotherapy with autologous stem-cell support (HDCT-ASCT), resulting in 2-year progression-free (PFS) and overall survival (OS) of 60·6% and 67·9%...
June 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28641632/-clinical-efficacy-of-epoch%C3%A2-r-followed-by-dice%C3%A2-r-regimen-for-primary-breast-diffuse-large-b-cell-lymphoma
#5
Li-Hua Dong, Jian-Lin Chen, Xue Gao, Gang-Ping Li, Yu-Fu Li, Yong-Ping Song, Xu-Dong Wei
OBJECTIVE: To explore the clinical efficacy and safety of EPOCH±R followed by DICE±R regimen for primary breast diffuse large B-cell lymphoma. METHODS: Forty-three patients with primary breast diffuse large B-cell lymphoma were admitted in our hosptial from January 2000 to April 2016. Among them 24 patients were treated with CHOP±R regimen, 19 patients were treated with EPOCH±R followed by DICE±R regimen. The clinical efficacy, survival rate and adverse effects were observed and compared between them...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641631/-characteristics-and-prognostic-significance-of-cytogenetic-abnormalities-in-diffuse-large-b-cell-lymphoma-patients-with-bone-marrow-involvement
#6
Wei Liu, Rui Lyu, Wen-Yang Huang, Cheng-Wen Li, Hong Liu, Jian Li, De-Hui Zou, Lu-Gui Qiu, Shu-Hua Yi
OBJECTIVE: To investigate the cytogenetic abnormalitis in patients with diffuse large B-cell lymphoma(DLBCL) patients with bone marrow involvement and their influence on prognosis. METHODS: Conventional karyotyping was performed on bone marrow specimens in 47 DLBCL patients with histologically confirmed bone marrow involvement(BMI). The karyotyping results of bone marrow, the characteristics and clinical effect of chromosomal abnormalities were analysed. RESULTS: In 47 DLBCL cases with BMI, the chromosomal abnormalities were detected in 25(53%) cases...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28640256/microrna-26a-cyclin-dependent-kinase-5-axis-controls-proliferation-apoptosis-and-in-vivo-tumor-growth-of-diffuse-large-b-cell-lymphoma-cell-lines
#7
Floriana Maria Farina, Alessandra Inguscio, Paolo Kunderfranco, Alice Cortesi, Leonardo Elia, Manuela Quintavalle
Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of non-Hodgkin lymphoma. Despite a favorable therapeutic response to first-line chemo-immunotherapy, still 30-40% of patients is refractory, or relapse after this treatment. Thus, alternative strategies must be sought. Previous studies have indicated that cyclin-dependent kinase 5 (CDK5), a serine/threonine protein kinase, is involved in tumor development and progression, and it may represent a potential therapeutic target. However, its role in modulating DLBCL growth and progression remains largely unexplored...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28640132/treatment-outcome-of-diffuse-large-b-cell-lymphoma-involving-the-head-and-neck-two-institutional-study-for-the-significance-of-radiotherapy-after-r-chop-chemotherapy
#8
Yoo-Kang Kwak, Byung-Ock Choi, Sung Hwan Kim, Joo Hwan Lee, Dae Gyu Kang, Jong Hoon Lee
This study was performed to analyze the treatment outcome for diffuse large B-cell lymphoma (DLBCL) involving the head and neck and to evaluate the role of radiotherapy in the rituximab era. Fifty-six patients diagnosed with DLBCL involving the head and neck were assessed. All patients were treated with 6 cycles of rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone (R-CHOP). After chemotherapy, radiation was delivered to the head and neck area in a median dose of 36 Gy. Radiation was delivered using 3-dimensional radiotherapy (n  =  25) or intensity-modulated radiotherapy (n  =  31)...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28639315/myc-protein-dysregulation-is-driven-by-bcr-pi3k-signaling-in-diffuse-large-b-cell-lymphoma
#9
Wei-Ge Wang, Ze-Bing Liu, Xiang-Nan Jiang, Jimmy Lee, Xiao-Yan Zhou, Xiao-Qiu Li
INTRODUCTION: MYC overexpression is a common feature of diffuse large B-cell lymphoma (DLBCL) and is associated with poor prognosis in patients with this neoplasm. The underlying mechanisms of MYC dysregulation, however, have not been fully understood. MATERIALS AND METHODS: We immunohistochemically evaluated the correlation between BCR-PI3K pathway activity and MYC protein level in 108 cases of de novo DLBCL, twenty five of which featured loss of B-cell receptor (BCR-negative), and investigated the effects of BCR-PI3K signaling on MYC protein level and phosphorylation in DLBCL cell lines...
June 21, 2017: Histopathology
https://www.readbyqxmd.com/read/28639256/response-and-survival-benefit-with-chemoimmunotherapy-in-epstein-barr-virus-positive-diffuse-large-b-cell-lymphoma
#10
Brady E Beltran, Pilar Quiñones, Domingo Morales, Jose M Malaga, Julio C Chavez, Eduardo M Sotomayor, Jorge J Castillo
Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a haematologic malignancy with poor prognosis when treated with chemotherapy. We evaluated response and survival benefits of chemoimmunotherapy in EBV-positive DLBCL patients. A total of 117 DLBCL patients were included in our retrospective analysis; 33 were EBV-positive (17 treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] and 16 with CHOP), and 84 were EBV-negative (all treated with R-CHOP)...
June 22, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28638688/spontaneous-regression-of-epstein-barr-virus-associated-lymphoproliferative-disorder-in-a-juvenile-idiopathic-arthritis-patient-after-the-discontinuation-of-methotrexate-and-etanercept
#11
Ariane Klein, Harald Reinhard, Annette M Mueller, Gerd Horneff
A case of a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) since the age of 4 years is reported here. This patient also suffered from multiple congenital anomalies. On long-term treatment with oral methotrexate (MTX) and etanercept, multiple subcutaneous nodules were detected, which were accompanied by increased lactate dehydrogenase and uric acid levels. A biopsy of the largest nodule revealed Epstein-Barr (EB) virus-positive diffuse large B-cell lymphoma (DLBCL). The patient was classified as clinical stage IIIA due to a mediastinal lesion...
June 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/28637496/mir21-sensitized-b-lymphoma-cells-to-abt-199-via-icos-icosl-mediated-interaction-of-treg-cells-with-endothelial-cells
#12
Zhong Zheng, Peng-Peng Xu, Li Wang, Hui-Jin Zhao, Xiang-Qin Weng, Hui-Juan Zhong, Bin Qu, Jie Xiong, Yan Zhao, Xue-Feng Wang, Anne Janin, Wei-Li Zhao
BACKGROUND: MicroRNAs (miRs) are involved in tumor progression by regulating tumor cells and tumor microenvironment. MiR21 is overexpressed in diffuse large B-cell lymphoma (DLBCL) and its biological impact on tumor microenvironment remains unclear. METHODS: MiR21 was assessed by quantitative RT-PCR in patients with newly diagnosed DLBCL. The mechanism of action of miR21 on lymphoma progression and tumor angiogenesis was examined in vitro in B-lymphoma cell lines and in vivo in a murine xenograft model...
June 21, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28633038/hematopoietic-cell-transplantation-for-diffuse-large-b-cell-and-follicular-lymphoma-current-controversies-and-advances
#13
REVIEW
Narendranath Epperla, Mehdi Hamadani
Non-Hodgkin's lymphoma (NHL) constitutes a collection of lymphoproliferative disorders with diverse biologic, histologic, and clinical features. With a better understanding of the molecular pathogenesis, recently there have been major advances in the treatment of NHLs including addition of novel monoclonal antibodies, targeted therapies, and immune activators to the therapy armamentarium. Despite these remarkable developments, autologous hematopoietic cell transplantation (auto-HCT) remains not only a standard-of-care curative option for aggressive NHL but also an important therapeutic option for indolent NHL...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28629825/ict1-predicts-a-poor-survival-and-correlated-with-cell-proliferation-in-diffuse-large-b-cell-lymphoma
#14
Wenjun Xie, Meijuan Wu, Tianhong Fu, Xiaohong Li, Zhaoming Wang, Yongxian Hu, Liyan Zhu, Gu Zhang
Immature colon carcinoma transcript-1 (ICT1) is a crucial member of the large mitoribosomal subunit in mitochondrial ribosome, which has been shown to be closely related to tumorigenesis. Its expression and function in human diffuse large B-cell lymphoma (DLBCL), however, remained elusive. In this study, analysis of public available Oncomine database suggested that the expression levels of ICT1 mRNA was significantly upregulated in DLBCL tissues. Consistently, we described ICT1 was remarkably upregulated in fresh DLBCL samples compared with the corresponding normal tissues using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting...
June 16, 2017: Gene
https://www.readbyqxmd.com/read/28629257/risk-stratification-of-diffuse-large-b-cell-lymphoma-with-interim-pet-ct-based-on-different-cutoff-deauville-scores
#15
Jihyun Kim, Yoo Sung Song, Jong Seok Lee, Won Woo Lee, Sang Eun Kim
We evaluated the usefulness of interim (18)F-FDG PET/CT for risk stratification using different cutoff values of the Deauville 5-point scale (5-DS) in DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). One hundred and fifty patients underwent interim (I-) and end of treatment (EOT-) PET/CT scans. Applying the conventional 5-DS cutoff value of scores 4 to 5 at interim, there was no significant difference in progression free survival (PFS) between I-PET negative and I-PET positive patients...
June 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28627414/role-of-akt-hyperactivation-and-the-potential-of-akt-targeted-therapy-in-diffuse-large-b-cell-lymphoma
#16
Jinfen Wang, Zijun Y Xu-Monette, Kausar J Jabbar, Qi Shen, Ganiraju C Manyam, Alexandar Tzankov, Carlo Visco, Jing Wang, Santiago Montes-Moreno, Karen Dybkær, Wayne Tam, Govind Bhagat, Eric D Hsi, J Han van Krieken, Maurilio Ponzoni, Andrés J M Ferreri, Shi Wang, Michael B Møller, Miguel A Piris, L Jeffrey Medeiros, Yong Li, Lan V Pham, Ken H Young
AKT signaling is important for proliferation and survival of tumor cells. The clinical significance of AKT activation in diffuse large B-cell lymphoma (DLBCL) is not well analyzed. Here, we assessed expression of phosphorylated AKT (p-AKT) in 522 DLBCL patients. We found high levels of p-AKT nuclear expression, observed in 24.3% of the study cohort, were associated with significantly worse progression-free survival and Myc and Bcl-2 overexpression. However, multivariate analysis indicated that AKT hyperactivation was not an independent factor...
June 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28626260/a-case-of-api2-malt1-positive-gastric-malt-lymphoma-with-concomitant-diffuse-large-b-cell-lymphoma
#17
Akashi Fujita, Masahiro Tajika, Tsutomu Tanaka, Makoto Ishihara, Yutaka Hirayama, Nobumasa Mizuno, Kazuo Hara, Susumu Hijioka, Hiroshi Imaoka, Tsukasa Yoshida, Nozomi Okuno, Nobuhiro Hieda, Takashi Hirayama, Hitoshi Shibuya, Hisashi Kondo, Hirotaka Suzuki, Kazuhiro Toriyama, Yasushi Yatabe, Kenji Yamao, Yasumasa Niwa
API2-MALT1 translocation-positive gastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) lymphoma is thought to transform to diffuse large B-cell lymphoma (DLBCL) rarely. A 69-year-old man presented with epigastralgia. Esophagogastroduodenoscopy showed multiple ulcerations in the stomach. Endoscopic biopsies revealed MALT lymphoma, with Helicobacter pylori infection. The patient underwent eradication therapy with no improvement, and was thereafter followed without additional therapy at his request...
February 2017: Nagoya Journal of Medical Science
https://www.readbyqxmd.com/read/28623396/assessment-of-the-circulating-cell-free-dna-marker-association-with-diagnosis-and-prognostic-prediction-in-patients-with-lymphoma-a-single-center-experience
#18
Mao Li, Yongqian Jia, Juan Xu, Xiaomin Cheng, Caigang Xu
Circulating cell-free DNA (ccfDNA) has been shown to be associated with the clinical characteristics and prognosis of cancer patients. Our objective was to assess whether the concentration and integrity index of ccfDNA in plasma may be useful for diagnosing and monitoring the progression of patients with lymphoma. We included plasma samples from 174 lymphoma patients and 80 healthy individuals. The total concentration of ccfDNA was determined using a fluorometry method, and the DNA integrity index (DII), which is the ratio of longer to shorter DNA fragments, for the APP gene was detected using real-time quantitative PCR...
June 16, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28621491/outcome-of-patients-older-than-80%C3%A2-years-with-diffuse-large-b-cell-lymphoma-dlbcl-treated-with-standard-immunochemotherapy-a-large-retrospective-study-from-4-institutions
#19
Stefania Gobba, Alden A Moccia, Wiebke Gulden-Sala, Annarita Conconi, Stefan Diem, Luciano Cascione, Gloria Iacoboni, Gloria Margiotta-Casaluci, Kathrin Aprile von Hohenstaufen, Anastasios Stathis, Felicitas Hitz, Graziella Pinotti, Gianluca Gaidano, Emanuele Zucca
Little information is available on the very elderly patients with diffuse large B-cell lymphoma (DLBCL). We performed a retrospective analysis of 281 patients >80 years old with newly diagnosed DLBCL treated in 4 referral institutions in Switzerland and Northern Italy. Primary end points were overall survival, progression-free survival, and cause-specific survival. Systemic chemotherapy was given to 239 patients, and 119 of them received rituximab in their initial treatment. At a median follow-up of 5.5 years, 5-year progression-free survival was 26% (95% confidence interval [CI], 20-32%), 5-year overall survival was 31% (95% CI, 25-37%), and 5-year cause-specific survival was 48% (95% CI, 41-55%) for the entire cohort...
June 16, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28616658/high-kif2a-expression-predicts-unfavorable-prognosis-in-diffuse-large-b-cell-lymphoma
#20
Yaping Zhang, Xuefen You, Hong Liu, Mengqi Xu, Qingxiu Dang, Li Yang, Jianfei Huang, Wenyu Shi
Kinesin family member 2A (KIF2A), a conserved motor protein, plays a critical role in the pathogenesis and prognosis of several malignant tumors. The aim of the present study was to investigate KIF2A expression in diffuse large B cell lymphoma (DLBCL), evaluate the association between KIF2A expression and the clinical parameters of the disease, and determine its prognostic value. KIF2A expression was evaluated in 134 DLBCL and 57 reactive hyperplasia samples using immunohistochemistry on a tissue microarray...
June 14, 2017: Annals of Hematology
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