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Zhihong Hu, L Jeffrey Medeiros, Zi Chen, Weina Chen, Shaoying Li, Sergej N Konoplev, Xinyan Lu, Lan V Pham, Ken H Young, Wei Wang, Shimin Hu
MYC rearrangement in mantle cell lymphoma (MCL) is rare, and its clinicopathologic significance is not well defined. We report 17 cases of MCL with 8q24/MYC rearrangement, detected at the time of initial diagnosis of MCL in 10 patients and subsequently during the clinical course in 7 patients. There were 12 men and 5 women with a median age of 61 years (range, 49 to 81 y). Fourteen patients had lymphadenopathy (Ann Arbor stage III/IV), and 3 patients presented with a leukemic pattern without lymphadenopathy...
October 21, 2016: American Journal of Surgical Pathology
Sheng-Tsung Chang, Shang-Wen Chen, Chung-Han Ho, Chun-Chi Kuo, Seiji Sakata, Kengo Takeuchi, Shih-Sung Chuang
BACKGROUND/PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma type. The immunophenotypic and genetic features of DLBCL in Taiwan have not been characterized. METHODS: In this study, we performed immunohistochemical analysis and interphase fluorescence in situ hybridization (FISH) using tissue microarray sections to investigate a cohort of unselected DLBCL cases in a single institution in Taiwan from 1990 to 2010. RESULTS: Of the 153 cases investigated, CD10, bcl-6, and MUM1 were expressed in 16...
October 20, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Xuan J Wang, L Jeffrey Medeiros, Carlos E Bueso-Ramos, Guilin Tang, Sa Wang, Yasuhiro Oki, Parth Desai, Joseph D Khoury, Roberto N Miranda, Zhenya Tang, Nishitha Reddy, Shaoying Li
In patients with diffuse large B-cell lymphoma, MYC rearrangement (MYC-R), MYC expression, or concurrent expression of MYC and BCL2 is associated with a poorer prognosis. P53 expression also has been shown to confer inferior survival in diffuse large B-cell lymphoma patients, but less is known about the role of P53 expression in those with MYC-R, MYC expression (MYC+), or MYC&BCL2 co-expression (MYC+/BCL2+). We studied P53 expression in 201 patients with untreated de novo diffuse large B-cell lymphoma. Sixty-seven (33%) cases were P53 positive, 56 (28%) had MYC-R (including 17 MYC/BCL2 double hit lymphoma), 86 (45%) were MYC+/BCL2+, and 47 (24%) were positive for both MYC and P53...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Allison Rosenthal, Anas Younes
Diffuse large B-cell lymphomas with aberrations in MYC, BCL2 and/or BCL6 by genetic alterations or protein expression represent a group of high grade B-cell lymphomas with inferior outcomes when treated with standard RCHOP chemotherapy. As a result, intensified induction regimens have been suggested in an effort to improve outcomes. Conclusions to date have largely been drawn from retrospective data although prospective data is slowly starting to emerge. Chemoimmunotherapy refractoriness is problematic and relapse rates are high...
September 30, 2016: Blood Reviews
Marco Lucioni, Emilio Berti, Luca Arcaini, Giorgio A Croci, Aldo Maffi, Catherine Klersy, Gaia Goteri, Carlo Tomasini, Pietro Quaglino, Roberta Riboni, Mariarosa Arra, Elena Dallera, Vieri Grandi, Mauro Alaibac, Antonio Ramponi, Sara Rattotti, Maria Giuseppina Cabras, Silvia Franceschetti, Giulio Fraternali-Orcioni, Nicola Zerbinati, Francesco Onida, Stefano Ascani, Maria Teresa Fierro, Serena Rupoli, Marcello Gambacorta, Pier Luigi Zinzani, Nicola Pimpinelli, Marco Santucci, Marco Paulli
Categorization of primary cutaneous B-cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus-based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL...
September 26, 2016: Cancer Medicine
Gwyneth Soon, Guan Wei Ow, Hian Li Chan, Siok Bian Ng, Shi Wang
Primary cardiac lymphoma (PCL) is a rare extranodal lymphoma that involves only the heart and/or pericardium. Primary cardiac lymphoma is much less common in immunocompetent patients compared with those who are immunosuppressed. Patients with PCL have variable clinical manifestations that may lead to misdiagnosis and delay in treatment. Modern radiologic imaging now allows for earlier detection of these tumors. This study describes the clinical, histologic/cytologic, immunophenotypic, and molecular genetic findings for 3 immunocompetent patients with primary cardiac diffuse large B-cell lymphoma...
October 2016: Annals of Diagnostic Pathology
Mirei Horiuchi, Hoyuri Fuseya, Minako Tsutsumi, Yoshiki Hayashi, Kiyoyuki Hagihara, Hiroshi Kanashima, Takafumi Nakao, Yuko Fukushima, Takeshi Inoue, Takahisa Yamane
Double-hit lymphomas are rare tumors that are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint, mainly a t(14; 18)(q32;q21)involving BCL2. We report a case of a 38-yearold woman with a 2-month history of abdominaldistention. 18F-FDG PET showed multiple positive systemic lymph nodes, positive peritoneum, and multiple positive intra-abdominal masses. Histopathology results of the cervical lymph node were compatible with double-hit follicular lymphoma(Grade 3A)because fluorescence in situ hybridization(FISH)demonstrated both MYC rearrangement and BCL2 gene fusion...
September 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Mathilde Chevin, Clémence Guiraut, Caroline Maurice-Gelinas, Jessica Deslauriers, Sylvain Grignon, Guillaume Sébire
BACKGROUND: Despite the recent introduction of hypothermia as a mandatory standard of care, the incidence of neonatal encephalopathy in full-term newborns and its devastating neuro-behavioral outcomes continues to be a major individual, familial and social issue. Neonatal encephalopathy is mainly due to the compounding and interacting effects of hypoxia-ischemia and inflammation resulting from placental and other perinatal infections. It is unclear why hypothermia is effective in alleviating neonatal encephalopathy in some, but not all, full-term newborns...
September 9, 2016: International Journal of Developmental Neuroscience
Jung Yong Hong, Cheolwon Suh, Won Seog Kim
Various strategies have been implemented to improve the outcomes of diffuse large B-cell lymphoma (DLBCL). In recent years, remarkable advances have been achieved, based on the discovery of cell-of-origin in DLBCL and on more effective targeted agents. This commentary will summarize recent updates on the evolution of frontline therapies for DLBCL, focusing on the upcoming promising frontline chemotherapy platforms and on activated B-cell subtype DLBCL and double-hit DLBCL.
2016: F1000Research
Kimberlei A Richardson, Allison K Hester, Gabrielle L McLemore
As more states and countries legalize medical and/or adult recreational marijuana use, the incidences of Prenatal Cannabis Exposure (PCE) will likely increase. While young people increasingly view marijuana as innocuous, marijuana preparations have been growing in potency in recent years, potentially creating global clinical, public health, and workforce concerns. Unlike fetal alcohol spectrum disorder, there is no phenotypic syndrome associated with PCE. There is also no preponderance of evidence that PCE causes lifelong cognitive, behavioral, or functional abnormalities, and/or susceptibility to subsequent addiction...
August 24, 2016: Neurotoxicology and Teratology
Leili Shahriyari, Natalia L Komarova, Alexandra Jilkine
BACKGROUND: Colon and intestinal crypts serve as an important model system for adult stem cell proliferation and differentiation. We develop a spatial stochastic model to study the rate of somatic evolution in a normal crypt, focusing on the production of two-hit mutants that inactivate a tumor suppressor gene. We investigate the effect of cell division pattern along the crypt on mutant production, assuming that the division rate of each cell depends on its location. RESULTS: We find that higher probability of division at the bottom of the crypt, where the stem cells are located, leads to a higher rate of double-hit mutant production...
2016: Biology Direct
Yuan Miao, Shimin Hu, Xinyan Lu, Shaoying Li M D, Wei Wang, L Jeffrey Medeiros, Pei Lin
Follicular lymphoma (FL) with MYC and BCL2 translocations, so-called double-hit follicular lymphoma (DH-FL), is rare. Here we report the clinicopathologic features of 7 cases of DH-FL. All neoplasms had a follicular pattern (1 partially diffuse). Five cases were of predominantly low grade, 4 of which had focal (≤ 20%) grade 3 A areas, and 2 cases were of grade 3. All cases were positive for pan B-cell antigens, CD10 and BCL6; 6 cases were positive for BCL2. Ki67 was ≤50% in 6 cases and 90% in one grade 3 case...
August 17, 2016: Human Pathology
Ryota Kurimoto, Katsuhiro Shono, Masahiro Onoda, Kyohei Yamamoto, Akira Yokota
Several reports have suggested an increased risk of malignant lymphoma in patients with rheumatoid arthritis treated with methotrexate (MTX). We herein describe the case of a 71-year-old woman with rheumatoid arthritis who developed MYC/BCL2 double-hit lymphoma associated with MTX therapy. She developed a fever and lymphadenopathies over a 2-week period and had elevated levels of soluble IL-2 receptor. Inguinal lymph node and bone marrow biopsies showed diffuse large B cell lymphoma. Fluorescent in situ hybridization revealed MYC and BCL2 gene rearrangements in her lymphoma cells...
2016: Internal Medicine
Niels Weinhold, Cody Ashby, Leo Rasche, Shweta S Chavan, Caleb Stein, Owen W Stephens, Ruslana Tytarenko, Michael A Bauer, Tobias Meissner, Shayu Deshpande, Purvi H Patel, Timea Buzder, Gabor Molnar, Erich A Peterson, Frits van Rhee, Maurizio Zangari, Sharmilan Thanendrarajan, Carolina Schinke, Erming Tian, Joshua Epstein, Bart Barlogie, Faith E Davies, Christoph J Heuck, Brian A Walker, Gareth J Morgan
To elucidate the mechanisms underlying relapse from chemotherapy in multiple myeloma, we performed a longitudinal study of 33 patients entered into Total Therapy protocols investigating them using gene expression profiling, high-resolution copy number arrays, and whole-exome sequencing. The study illustrates the mechanistic importance of acquired mutations in known myeloma driver genes and the critical nature of biallelic inactivation events affecting tumor suppressor genes, especially TP53, the end result being resistance to apoptosis and increased proliferation rates, which drive relapse by Darwinian-type clonal evolution...
September 29, 2016: Blood
Daniel J Landsburg, Marissa K Falkiewicz, Adam M Petrich, Benjamin A Chu, Amir Behdad, Shaoying Li, L Jeffrey Medeiros, Ryan D Cassaday, Nishitha M Reddy, Martin A Bast, Julie M Vose, Kimberly R Kruczek, Scott E Smith, Priyank Patel, Francisco Hernandez-Ilizaliturri, Reem Karmali, Saurabh Rajguru, David T Yang, Joseph J Maly, Kristie A Blum, Weiqiang Zhao, Charles Vanslambrouck, Chadi Nabhan
Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC-amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with DHL, all treated with either R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy...
July 29, 2016: British Journal of Haematology
Mona Buhusi, Kaitlin Olsen, Benjamin Z Yang, Catalin V Buhusi
Maladaptive reactivity to stress is linked to improper decision making, impulsivity, and discounting of delayed rewards. Chronic unpredictable stress (CUS) alters dopaminergic function, re-shapes dopaminergic circuits in key areas involved in decision making, and impairs prefrontal-cortex dependent response inhibition and working memory. Glial-derived neurotrophic factor (GDNF) is essential for regulating dopamine (DA) release in the basal ganglia and for the survival of dopaminergic neurons; GDNF-deficient mice are considered an animal model for aging-related Parkinsonism...
2016: Frontiers in Behavioral Neuroscience
Miriam Kalbitz, Michael Karbach, Sonja Braumueller, Philipp Kellermann, Florian Gebhard, Markus Huber-Lang, Mario Perl
BACKGROUND: Severe blunt chest trauma is associated with high mortality. Sepsis represents a serious risk factor for mortality in acute respiratory distress syndrome (ARDS). In septic patients with ARDS complement activation products were found to be elevated in the plasma. In single models like LPS or trauma complement has been studied to some degree, however in clinically highly relevant double hit models such as the one used here little data is available. Here, we hypothesized that absence of C5 is correlated with a decreased inflammatory response in trauma induced septic acute lung injury...
2016: PloS One
Joaquín Araos, Leyla Alegría, Patricio García, Felipe Damiani, Pablo Tapia, Dagoberto Soto, Tatiana Salomon, Felipe Rodriguez, Macarena Amthauer, Benjamín Erranz, Gabriel Castro, Pamela Carreño, Tania Medina, Jaime Retamal, Pablo Cruces, Guillermo Bugedo, Alejandro Bruhn
Extracorporeal membrane oxygenation (ECMO) is increasingly being used to treat severe acute respiratory distress syndrome (ARDS). However, there is limited clinical evidence about how to optimize the technique. Experimental research can provide an alternative to fill the actual knowledge gap. The purpose of the present study was to develop and validate an animal model of acute lung injury (ALI) which resembled severe ARDS, and which could be successfully supported with ECMO. Eighteen pigs were randomly allocated into three groups: sham, ALI, and ALI + ECMO...
2016: American Journal of Translational Research
Natalia Testo, Luke C Olson, Shivakumar Subramaniyam, Ty Hanson, Cynthia M Magro
Aggressive extracutaneous B-cell lymphomas span the various stages of B-cell ontogeny and include B-cell lymphoblastic lymphoma, Burkitt lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma. Diffuse large B-cell lymphomas represent the most common histologic subtype of non-Hodgkin lymphomas, comprising 30% of adult non-Hodgkin lymphomas in the United States. A distinctive form of diffuse large B-cell lymphoma is the double-hit lymphoma, with most cases exhibiting a combined MYC and BCL2 rearrangement, leading some hematopathologists to propose the term MYC/BCL2 lymphoma...
October 2016: American Journal of Dermatopathology
Miaoxia He, Keting Chen, Suhong Li, Shimin Zhang, Jianming Zheng, Xiaoxia Hu, Lei Gao, Jie Chen, Xianmin Song, Weiping Zhang, Jianmin Wang, Jianmin Yang
BACKGROUND AND AIMS: Primary gastric B-cell lymphoma is the second most common malignancy of the stomach. There are many controversial issues about its diagnosis, treatment and clinical management. "Double-hit" and "double-protein" involving gene rearrangement and protein expression of c-Myc and bcl2/bcl6 are the most used terms to describe DLBCL poor prognostic factors in recent years. However, very little is known about the role of these prognostic factors in primary gastric B-cell lymphomas...
2016: Journal of Cancer
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