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Anahita Nosrati, Ahmad Monabati, Alireza Sadeghipour, Fatemeh Radmanesh, Akbar Safaei, Sajjadeh Movahedinia
Primary central nervous system lymphoma (PCNSL) is a rare specific subtype of non-Hodgkin lymphoma limited to the brain, leptomeninges, spinal cord, or eyes without any systemic presentation and relapse which mostly takes place in CNS. In more than 95% of patients, it is of diffuse large B cell lymphoma (DLBCL) type. Categorizing PCNSL to germinal center cell like or activated B cell like, as we usually do for DLBCL NOS, may not be applicable for predicting outcome. Possible prognostic significance of MYC, BCL2, and/or BCL6 rearrangements may be important given what we know about their impact in systemic DLBCL, but we have limited knowledge about the status of double or triple hit molecular changes in PCNSL...
October 11, 2018: Annals of Hematology
Karim Rihawi, Roberta Alfieri, Michelangelo Fiorentino, Francesca Fontana, Elisa Capizzi, Andrea Cavazzoni, Mario Terracciano, Silvia La Monica, Alberto Ferrarini, Genny Buson, Pier Giorgio Petronini, Andrea Ardizzoni
INTRODUCTION: Translocations of the anaplastic lymphoma kinase (ALK) can be effectively targeted in advanced non-small cell lung cancer by ALK-TKI inhibitors including Crizotinib. However, the development of acquired resistance often limits the duration of these therapies. While several mechanisms of secondary resistance have been already identified, little is known about molecular determinants of primary resistance. In our brief report we investigated the tumor molecular profile of a patient who failed to respond to Crizotinib...
October 2, 2018: Translational Oncology
Pekka Peroja, Mette Pedersen, Tuomo Mantere, Peter Nørgaard, Jenni Peltonen, Kirsi-Maria Haapasaari, Jan Böhm, Esa Jantunen, Taina Turpeenniemi-Hujanen, Katrin Rapakko, Peeter Karihtala, Ylermi Soini, Kaija Vasala, Outi Kuittinen
Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with diverse outcomes. Concurrent translocation of MYC and BCL-2 and/or BCL-6, and concurrent immunohistochemical (IHC) high expression of MYC and BCL-2, have been linked to unfavorable treatment responses. TP53-mutated DLBCL has also been linked to worse outcome. Our aim was to evaluate the aforementioned issues in a cohort of 155 patients uniformly treated with R-CHOP-like therapies. We performed direct sequencing of TP53 exons 5, 6, 7 and 8 as well as fluorescence in-situ hybridization (FISH) of MYC, BCL-2 and BCL-6, and IHC of MYC, BCL-2 and BCL-6...
October 4, 2018: Scientific Reports
Jie Huang, Dongxian Jiang, Ting Zhu, Yanqiu Wang, Hao Wang, Qun Wang, Lijie Tan, Hongguang Zhu, Yingyong Hou, Junxia Yao
BACKGROUND: We investigated the frequency of c-MYC amplification in esophageal squamous cell carcinoma (ESCC), including both stage I-II and III-IVa disease, and evaluated the correlation of c-MYC amplification with clinicopathologic parameters and outcome. METHODS: In 259 ESCC resected at Zhongshan Hospital, Fudan University from January 2007 to November 2010, c-MYC amplification was analyzed using tissue microarray, with fluorescence in situ hybridization (FISH) assay...
September 28, 2018: Annals of Thoracic Surgery
Saihong Yan, Miao Wang, Xuefang Liang, Christopher J Martyniuk, Jinmiao Zha, Zijian Wang
To assess hepatotoxicity and to determine the underlying mechanisms of carbamazepine (CBZ) toxicity in fish, histopathology and the liver proteome were examined after Chinese rare minnow (Gobiocypris rarus) were exposed to 1, 10, and 100 μg/L CBZ for 28 days. Histopathological changes included disruption of spatial structure, pyknotic nuclei, cellular vacuolization and deformation of cell nuclei, in addition to marked swelling of hepatocytes in all treatment groups. Protein analysis revealed that there were gender-specific responses in rare minnow following exposure, and there were 47 proteins in females and 22 proteins in males identified as differentially abundant following CBZ treatments...
December 2018: Environmental Pollution
Asaad Azarnezhad, Mina Tabrizi, Firouzeh Javan, Parvin Mehdipour
Background/aim: The aims of this study were to detect CCND1 , C-MYC , and FGFR1 amplification using qPCR, confirmation with FISH, and to further assess their clinicopathological relevance. Materials and methods: Thirty-five breast tumor samples were analyzed for amplification of the selected genes using modified SYBR Green qPCR. The accuracy of the qPCR was assessed by FISH as a gold-standard method. Results: CCND1 , C-MYC , and FGFR1 amplifications were observed in 34...
August 16, 2018: Turkish Journal of Medical Sciences
Anne M R Schrader, Patty M Jansen, Maarten H Vermeer, Johanna K Kleiverda, Joost S P Vermaat, Rein Willemze
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) and primary cutaneous follicle center lymphoma (PCFCL) are cutaneous B-cell lymphomas (CBCL) with different clinical characteristics and behavior. PCDLBCL-LT is the most aggressive CBCL with a relatively poor prognosis. In nodal diffuse large B-cell lymphoma (DLBCL), rearrangements of the MYC gene, especially in combination with a second hit in BCL2 and/or BCL6, and double protein expression of MYC and BCL2 (DE) are adverse prognostic factors...
November 2018: American Journal of Surgical Pathology
Chiara Borga, Gilseung Park, Clay Foster, Jessica Burroughs-Garcia, Matteo Marchesin, Rikin Shah, Ameera Hasan, Syed T Ahmed, Silvia Bresolin, Lance Batchelor, Teresa Scordino, Rodney R Miles, Geertruy Te Kronnie, James L Regens, J Kimble Frazer
Precursor-B cell acute lymphoblastic leukemia (pre-B ALL) is the most common pediatric cancer, but there are no useful zebrafish pre-B ALL models. We describe the first highly- penetrant zebrafish pre-B ALL, driven by human MYC. Leukemias express B lymphoblast-specific genes and are distinct from T cell ALL (T-ALL)-which these fish also develop. Zebrafish pre-B ALL shares in vivo features and expression profiles with human pre-B ALL, and these profiles differ from zebrafish T-ALL or normal B and T cells. These animals also exhibit aberrant lymphocyte development...
August 15, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Fuli Yao, Licheng Yin, Shiyu Feng, Xinyan Wang, Anying Zhang, Hong Zhou
In mammals, both runt-related transcription factor 3 (RUNX3) and c-Myc are the downstream effectors of transforming growth factor-β1 (TGF-β1) signaling to mediate various cellular responses. However, information of their interaction especially in fish is lacking. In the present study, grass carp (Ctenopharyngodon idella) runx3 (gcrunx3) cDNA was cloned and identified. Interestingly, opposing effects of recombinant grass carp TGF-β1 (rgcTGF-β1) on c-myc and runx3 mRNA expression were observed in grass carp periphery blood lymphocytes (PBLs)...
August 10, 2018: Fish & Shellfish Immunology
Tarek Eldessouki, Kelly Hanley, Fatima Hamadeh, Olaronke O Oshilaja, Charles D Sturgis
The Revised fourth Edition World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues suggests novel categories, including "high grade B-cell lymphoma with MYC and BCL2 and BCL6 gene rearrangements." These diseases are known colloquially as "double hit" and "triple hit" lymphomas. The "first-hit" in these cases is the harboring of a MYC rearrangement. Concurrent derangements of BCL2 and BCL6 can be the "second-hit" or "third-hit...
July 25, 2018: Diagnostic Cytopathology
Mikiko Ise, Hajime Kageyama, Dai Ikebe, Akinobu Araki, Kyoya Kumagai, Makiko Itami
Follicular lymphoma (FL) is genetically characterized by BCL2/IGH translocation. Some FL cases histologically transform to high-grade lymphoma, and the majority of cases transform to diffuse large B-cell lymphoma. We report herein an unusual FL case that transformed to plasmablastic lymphoma (PBL) with MYC gene rearrangement as early as 12 months after FL diagnosis. IGH/MYC translocation, the most common cytogenetic abnormality seen in de novo PBL, was also detected in the transformed tumor (double-hit lymphoma)...
July 14, 2018: Journal of Clinical and Experimental Hematopathology: JCEH
Shaoying Li, Pei Lin, L Jeffrey Medeiros
The designation high-grade B-cell lymphoma (HGBL) has been incorporated into the 2016 Revision of the WHO classification of lymphoid neoplasms and includes two types: (1) HGBL, not otherwise specified; and (2) HGBL with MYC and BCL2 and/or BCL6 rearrangements, also known as double or triple hit lymphoma (DHL/THL). These categories of lymphomas represent 1-2% of non-Hodgkin lymphomas and a considerable portion of DLBCL patients who are primary refractory to R-CHOP therapy. It corresponds to the designation 'B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma' in the 2008 WHO classification...
August 2018: Expert Review of Hematology
Ehsan Pashay Ahi, Kristina M Sefc
Variation in fin shape and size contributes to the outstanding morphological diversity of teleost fishes, but the regulation of fin growth has not yet been studied extensively outside the zebrafish model. A previous gene expression study addressing the ornamental elongations of unpaired fins in the African cichlid fish Neolamprologus brichardi identified three genes (cx43, mmp9 and sema3d) with strong and consistent expression differences between short and elongated fin regions. Remarkably, the expression patterns of these genes were not consistent with inferences on their regulatory interactions in zebrafish...
June 25, 2018: Scientific Reports
Steven M Johnson, Jayadev Manikkam Umakanthan, Ji Yuan, Yuri Fedoriw, R Gregory Bociek, Kathleen Kaiser-Rogers, Jennifer N Sanmann, Nathan D Montgomery
High-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements, "double hit" or "triple hit" lymphomas (DTHL), are aggressive neoplasms associated with a poor prognosis. A t(3;8)(q27;q24) rarely occurs in B-cell lymphomas that results in a unique "pseudo-double hit" BCL6-MYC fusion, indistinguishable by interphase fluorescence in situ hybridization (FISH) from more conventional DTHL with independent MYC and BCL6 translocations. Reports of t(3;8)(q27;q24) lymphomas are sparse, and to better characterize their pathologic, cytogenetic, and clinical features, 6 new cases from 2 institutions and 19 previously published cases were reviewed...
June 11, 2018: Human Pathology
Alison M Moore, Olga Moshkin, Gordon J Swain, Susan Crocker, David P LeBrun
BACKGROUND: We report the first case of composite lymphoma consisting of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL) and high-grade B-cell lymphoma with MYC and BCL2 rearrangements within the same needle biopsy in which a clonal relationship between the FL and high-grade B-cell lymphoma components was demonstrated by molecular cytogenetics. CASE PRESENTATION: An 85-year-old man presented with masses in his neck and right groin...
May 24, 2018: Diagnostic Pathology
Xiao Yi Zhou, Xinyan Lu, Kirtee Raparia, Yi-Hua Chen
Purpose: Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL) after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy. Observations: A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.9 cm orbital mass. Histological section revealed a CD10-positive large B-cell lymphoma, consistent with transformation of FL...
June 2018: American Journal of Ophthalmology Case Reports
Heba Zayed, Iver Petersen
BACKGROUND: SOX2 has gained considerable interest as a pluripotency inducing gene. Co-transfection of SOX2 together with NANOG, KLF4 and c-MYC into adult fibroblasts was able to generate pluripotent stem cells. SOX2 has been reported to be expressed in synovial sarcoma, a tumor being characterized by the SS18-SSX gene fusion forming part of the SWI/SNF chromatin remodeling complex that affects histone methylation. The role of SOX2 in this tumor type as well as other soft tissue tumor entities however is still poorly characterized...
July 2018: Pathology, Research and Practice
Yu-Feng Song, Xiao-Ying Tan, Ya-Xiong Pan, Li-Han Zhang, Qi-Liang Chen
Although several studies have been conducted to study leptin function, information is very scarce on the molecular mechanism of leptin in fatty acid β-oxidation and oocytes maturation in fish. In this study, we investigated the potential role of fatty acid β-oxidation in leptin-mediated oocytes maturation in Pelteobagrus fulvidraco . Exp. 1 investigated the transcriptomic profiles of ovary and the differential expression of genes involved in β-oxidation and oocytes maturation following rt-hLEP injection; rt-hLEP injection was associated with significant changes in the expression of genes, including twenty-five up-regulated genes ( CPT1 , Acsl , Acadl , Acadm , Hadhb , Echsl , Hsd17b4 , Acca , PPARα , CYP8B1 , ACOX1 , ACBP , MAPK , RINGO , Cdc2 , MEK1 , IGF-1R , APC/C, Cdk2 , GnRHR, STAG3 , SMC1 , FSHβ and C-Myc ) and ten down-regulated gene ( PPARγ , FATCD36 , UBC , PDK1 , Acads , Raf , Fizzy , C3H-4 , Raf and PKC ), involved in fatty acid β-oxidation and oocytes maturation...
May 14, 2018: International Journal of Molecular Sciences
Thomas Adams, Deborah Fuchs, Patricia K Shadoan, Laurel Johnstone, Branden M Lau, Lee McGhan, Faiz Anwer, Hussam Al-Kateb
High grade B-cell lymphoma (HGBCL) by WHO 2016 classification requires rearrangements of MYC and BCL2 and/or BCL6, practically covering the so called "double-hit" or "triple hit" lymphomas. We report a case of HGBCL "triple-hit" lymphoma in a 64-year old female. Cytogenetic and fluorescence in situ hybridization (FISH) studies revealed complex karyotype including rearrangement of MYC to a novel, non-IG partner on chromosome 18, and rearrangement of BCL2, BCL6 and IGH as well as ins(3)(q21q27...
April 2018: Cancer Genetics
Hany Sakr, James R Cook
Aggressive lymphomas with MYC and BCL2 and/or BCL6 translocations ("double hit" lymphomas, DHL) represent a distinct diagnostic category in the updated World Health Organization (WHO) classification. The diagnostic yield of MYC immunohistochemistry (IHC) for the identification of DHL is currently uncertain. MYC IHC was performed in 272 consecutive cases of aggressive B-cell lymphoma, and results correlated with fluorescence in situ hybridization (FISH) for MYC translocations. Among 156 patients with IHC and FISH data, MYC IHC identified MYC translocations with 89% sensitivity, 38% specificity, 92% negative predictive value, and 29% positive predictive value...
April 7, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
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