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https://www.readbyqxmd.com/read/29786757/copy-number-abnormality-of-acute-lymphoblastic-leukemia-cell-lines-based-on-their-genetic-subtypes
#1
Chihiro Tomoyasu, Toshihiko Imamura, Toshihiro Tomii, Mio Yano, Daisuke Asai, Hiroaki Goto, Akira Shimada, Masashi Sanada, Shotaro Iwamoto, Junko Takita, Masayoshi Minegishi, Takeshi Inukai, Kanji Sugita, Hajime Hosoi
In this study, we performed genetic analysis of 83 B cell precursor acute lymphoblastic leukemia (B-ALL) cell lines. First, we performed multiplex ligation-dependent probe amplification analysis to identify copy number abnormalities (CNAs) in eight genes associated with B-ALL according to genetic subtype. In Ph+ B-ALL cell lines, the frequencies of IKZF1, CDKN2A/2B, BTG1, and PAX5 deletion were significantly higher than those in Ph- B-ALL cell lines. The frequency of CDKN2A/2B deletion in KMT2A rearranged cell lines was significantly lower than that in non-KMT2A rearranged cell lines...
May 21, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29781860/utility-of-immunohistochemistry-in-distinguishing-primary-adnexal-carcinoma-from-metastatic-breast-carcinoma-to-skin-and-squamous-cell-carcinoma
#2
Aida Valencia-Guerrero, Karen Dresser, Kristine M Cornejo
The distinction between primary adnexal carcinoma (PAC) from metastatic breast carcinoma (BrCa) to skin and squamous cell carcinoma (SCC), particularly those with ductal differentiation (SCCDD), can be quite challenging, despite adequate history. The aim of the study was to determine the utility of an immunohistochemistry (IHC) panel to differentiate these entities and apply them to ambiguous tumors. Twenty-seven PAC, 7 metastatic BrCa, 28 SCC, and 16 ambiguous cases (SCCDD vs. PAC, n = 13 and metastatic BrCa vs...
June 2018: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/29757368/the-long-noncoding-rna-landscape-of-neuroendocrine-prostate-cancer-and-its-clinical-implications
#3
Varune Rohan Ramnarine, Mohammed Alshalalfa, Fan Mo, Noushin Nabavi, Nicholas Erho, Mandeep Takhar, Robert Shukin, Sonal Brahmbhatt, Alexander Gawronski, Maxim Kobelev, Mannan Nouri, Dong Lin, Harrison Tsai, Tamara L Lotan, R Jefferey Karnes, Mark A Rubin, Amina Zoubeidi, Martin E Gleave, Cenk Sahinalp, Alexander W Wyatt, Stanislav V Volik, Himisha Beltran, Elai Davicioni, Yuzhuo Wang, Colin C Collins
Background: Treatment induced neuroendocrine prostate cancer (tNEPC) is an aggressive variant of late-stage metastatic castrate resistant (mCRPC) prostate cancer that commonly arises through neuroendocrine transdifferentiation (NEtD). Treatment options are limited, ineffective, and for most patients, results in death in less than a year. We previously developed a first-in-field patient-derived xenograft (PDX) model of NEtD. Longitudinal deep transcriptome profiling of this model enabled monitoring of dynamic transcriptional changes during NEtD and in the context of androgen deprivation...
May 10, 2018: GigaScience
https://www.readbyqxmd.com/read/29713018/a-pax5-oct4-prdm1-developmental-switch-specifies-human-primordial-germ-cells
#4
Fang Fang, Benjamin Angulo, Ninuo Xia, Meena Sukhwani, Zhengyuan Wang, Charles C Carey, Aurélien Mazurie, Jun Cui, Royce Wilkinson, Blake Wiedenheft, Naoko Irie, M Azim Surani, Kyle E Orwig, Renee A Reijo Pera
Dysregulation of genetic pathways during human germ cell development leads to infertility. Here, we analysed bona fide human primordial germ cells (hPGCs) to probe the developmental genetics of human germ cell specification and differentiation. We examined the distribution of OCT4 occupancy in hPGCs relative to human embryonic stem cells (hESCs). We demonstrated that development, from pluripotent stem cells to germ cells, is driven by switching partners with OCT4 from SOX2 to PAX5 and PRDM1. Gain- and loss-of-function studies revealed that PAX5 encodes a critical regulator of hPGC development...
April 30, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29678441/acute-lymphoblastic-leukemia-lymphoma-of-the-oral-and-maxillofacial-region
#5
Celeste Sánchez-Romero, Hélder Antônio Rebelo Pontes, Flávia Sirotheau Corrêa Pontes, André Caroli Rocha, Román Carlos, Javier C Rendón, Oslei Paes de Almeida, Felipe Paiva Fonseca
OBJECTIVE: Our objective was to describe the clinicopathologic and immunohistochemical features of acute lymphoblastic leukemia/lymphoma (ALL/LBL) of the oral and maxillofacial region (OMF). STUDY DESIGN: Cases diagnosed as ALL/LBL of the OMF region were retrieved from the files of 2 Brazilian and 1 Guatemalan oral pathology services from 2005 to 2017. Microscopic and immunohistochemical features of each case were reviewed and fully described, and clinical data were retrieved from the pathology reports...
January 31, 2018: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/29598887/expression-of-programmed-cell-death-1-programmed-cell-death-ligand-1-in-the-tumor-microenvironments-of-primary-gastrointestinal-diffuse-large-b-cell-lymphomas
#6
Yang Liu, Jing Ma, Kangjie Yu, Mingyang Li, Fang Liu, Qingguo Yan, Zhe Wang, Shuangping Guo
BACKGROUND: Gastrointestinal diffuse large B cell lymphoma (GI DLBCL) is the most common gastrointestinal lymphoma. However, there has not been a comprehensive investigation into the expression patterns of programmed cell death 1 (PD-1) and programmed cell death ligand 1(PD-L1) in GI DLBCL tissues. METHODS: PD-1 protein expression in tumor-infiltrating lymphocytes (TILs) was evaluated by immunohistochemical staining, and expression of PD-L1 was evaluated by using PD-L1/PAX5 immunohistochemical double staining in 92 GI DLBCL specimens...
March 12, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29581595/elevated-dna-methylation-in-malignant-tumors-of-the-sinonasal-tract-and-its-association-with-patient-survival
#7
Marcela Chmelarova, Jan Laco, Helena Kovarikova, Ivana Baranova, Pavel Dundr, Kristyna Nemejcova, Jaroslav Michalek, Milan Vosmik, Vladimir Palicka
BACKGROUND: Epigenetic modifications have been recognized as an important mechanism underlying carcinoma progression. DNA methylation plays an important role in cancer biology and represents potentially heritable changes in gene expression that do not involve DNA sequence. The aim of this study was to investigate promoter methylation of selected genes in sinonasal carcinoma by comparison with noncancerous sinonasal tissue. METHODS: To search for epigenetic events (methylation in 25 tumor suppressor genes) we used MS-MLPA (Methylation-specific multiplex ligation-dependent probe amplification) to compare methylation status of 59 formalin fixed, paraffin embedded tissue samples of sinonasal carcinomas with 18 control samples...
March 27, 2018: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/29580085/monitoring-minimal-residual-disease-in-canine-lymphomas-treated-with-modified-l-cop-or-l-chop-protocols
#8
Sirintra Sirivisoot, Patharakrit Teewasutrakul, Somporn Techangamsuwan, Sirikachorn Tangkawattana, Anudep Rungsipipat
Heteroduplex polymerase chain reaction for antigen receptor rearrangements (hPARR) was developed to monitor minimal residual disease (MRD) in canine B- and T-cell lymphomas treated with the modified L-COP or L-CHOP protocol. Thirty-five dogs were recruited in this study and their neoplastic lineages were determined by immunophenotyping with Pax5 and CD3. Peripheral blood leukocytes were collected prior to and during chemotherapy in weeks 4, 9 and 13 to detect MRD by hPARR. Twenty-eight dogs (80%) had B-cell lymphoma while seven dogs (20%) had T-cell lymphoma...
March 2018: Acta Veterinaria Hungarica
https://www.readbyqxmd.com/read/29575541/simultaneous-detection-of-abl1-mutation-and-ikzf1-deletion-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-using-a-customized-target-enrichment-system-panel
#9
M Aoe, H Ishida, T Matsubara, S Karakawa, H Kawaguchi, K Fujiwara, K Kanamitsu, K Washio, K Okada, M Shibakura, A Shimada
INTRODUCTION: Recent clinical outcomes of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) vastly improved owing to tyrosine kinase inhibitor (TKI). However, the genetic status would be different in each case with ABL1 gene mutation or copy number variants (CNVs) such as IKZF1 deletion. In particular, the TKI resistant clone with ABL1 kinase mutation remains problematic. The comprehensive assessment of genetic status including mutation, insertion and deletion (indel) and CNVs is necessary...
March 25, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29572766/cd3-cd56-eber1-atypical-extraosseous-plasmacytoma-of-the-nasal-cavity
#10
Yayoi Ando, Akiko Miyagi Maeshima, Suguru Fukuhara, Shinichi Makita, Wataru Munakata, Tatsuya Suzuki, Dai Maruyama, Hirokazu Taniguchi, Koji Izutsu
We present a case of atypical extraosseous plasmacytoma (EP) with a plasmablastic morphology and CD3+ CD56+ Epstein-Barr virus-encoded RNA-1 (EBER1)+ phenotypes of the nasal cavity. A 51-year-old male attended a local hospital with a tumor located in his left nasal cavity that was histologically diagnosed as extranodal NK/T cell lymphoma, nasal type. We reviewed the specimens and re-biopsied the tumor, and confirmed that the tumor was positive for CD3, CD56, and EBER1; however, the tumor showed a plasmablastic morphology without necrosis and angiocentricity, and was positive for CD138, but negative for CD20 and PAX5...
March 23, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29561272/novel-finding-of-paired-box-5-pax5-cytoplasmic-staining-in-well-differentiated-rectal-neuroendocrine-tumors-carcinoids-and-its-diagnostic-and-potentially-prognostic-utility
#11
Zhiyan Fu, Chunlai Zuo, Christine E Sheehan, Deepa T Patil, Jingmei Lin, Zhaohai Yang, Hwajeong Lee
Although nuclear immunostaining for paired box protein (PAX5) is widely used in practice, its cytoplasmic localization has not been evaluated. Recently we encountered cytoplasmic granular PAX5 staining in rectal well-differentiated neuroendocrine tumor (WD-NET) in the absence of nuclear staining. We investigated the specificity of this staining pattern for rectal NET (n=21) in comparison with 108 NETs, 1 WD rectal NET with elevated proliferation (WD-NET G3), and 40 poorly differentiated neuroendocrine carcinomas from the gastrointestinal and pancreatobiliary tract and liver...
March 20, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29552179/prognostic-significance-of-copy-number-alterations-detected-by-multi-link-probe-amplification-of-multiple-genes-in-adult-acute-lymphoblastic-leukemia
#12
Qiuyun Fang, Tian Yuan, Yan Li, Juan Feng, Xiaoyuan Gong, Qinghua Li, Xingli Zhao, Kaiqi Liu, Kejing Tang, Zheng Tian, Qi Zhang, Ying Wang, Bingcheng Liu, Min Wang, Kun Ru, Jianxiang Wang, Yingchang Mi
The multiplex ligation-dependent probe amplification (MLPA) method was used to detect the copy number alterations (CNAs) of IKAROS family zinc finger 1 ( IKZF1 ), paired box 5 ( PAX5 ), ETS variant 6 ( ETV6 ), RB transcriptional corepressor 1 ( RB1 ), BTG anti-proliferation factor 1 ( BTG1 ), early B-cell factor 1 ( EBF1 ), cyclin dependent kinase inhibitor 2A/2B ( CDKN2A/2B ) and cytokine receptor like factor 2 ( CRLF2 ) genes in 87 adults with acute lymphoblastic leukemia (ALL) in China. The effects of CNAs on prognosis were analyzed...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29551267/b-cell-specific-diversion-of-glucose-carbon-utilization-reveals-a-unique-vulnerability-in-b-cell-malignancies
#13
Gang Xiao, Lai N Chan, Lars Klemm, Daniel Braas, Zhengshan Chen, Huimin Geng, Qiuyi Chen Zhang, Ali Aghajanirefah, Kadriye Nehir Cosgun, Teresa Sadras, Jaewoong Lee, Tamara Mirzapoiazova, Ravi Salgia, Thomas Ernst, Andreas Hochhaus, Hassan Jumaa, Xiaoyan Jiang, David M Weinstock, Thomas G Graeber, Markus Müschen
B cell activation during normal immune responses and oncogenic transformation impose increased metabolic demands on B cells and their ability to retain redox homeostasis. While the serine/threonine-protein phosphatase 2A (PP2A) was identified as a tumor suppressor in multiple types of cancer, our genetic studies revealed an essential role of PP2A in B cell tumors. Thereby, PP2A redirects glucose carbon utilization from glycolysis to the pentose phosphate pathway (PPP) to salvage oxidative stress. This unique vulnerability reflects constitutively low PPP activity in B cells and transcriptional repression of G6PD and other key PPP enzymes by the B cell transcription factors PAX5 and IKZF1...
April 5, 2018: Cell
https://www.readbyqxmd.com/read/29507076/prognostic-impact-of-kinase-activating-fusions-and-ikzf1-deletions-in-pediatric-high-risk-b-lineage-acute-lymphoblastic-leukemia
#14
Thai Hoa Tran, Marian H Harris, Jonathan V Nguyen, Traci M Blonquist, Kristen E Stevenson, Eileen Stonerock, Barbara L Asselin, Uma H Athale, Luis A Clavell, Peter D Cole, Kara M Kelly, Caroline Laverdiere, Jean-Marie Leclerc, Bruno Michon, Marshall A Schorin, Jennifer J G Welch, Shalini C Reshmi, Donna S Neuberg, Stephen E Sallan, Mignon L Loh, Lewis B Silverman
Recurrent chromosomal rearrangements carry prognostic significance in pediatric B-lineage acute lymphoblastic leukemia (B-ALL). Recent genome-wide analyses identified a high-risk B-ALL subtype characterized by a diverse spectrum of genetic alterations activating kinases and cytokine receptor genes. This subtype is associated with a poor prognosis when treated with conventional chemotherapy but has demonstrated sensitivity to the relevant tyrosine kinase inhibitors. We sought to determine the frequency of kinase-activating fusions among National Cancer Institute (NCI) high-risk, Ph-negative, B-ALL patients enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 05-001 and to describe their associated clinical characteristics and outcomes...
March 13, 2018: Blood Advances
https://www.readbyqxmd.com/read/29498923/ikzf1-plus-defines-a-new-minimal-residual-disease-dependent-very-poor-prognostic-profile-in-pediatric-b-cell-precursor-acute-lymphoblastic-leukemia
#15
Martin Stanulla, Elif Dagdan, Marketa Zaliova, Anja Möricke, Chiara Palmi, Giovanni Cazzaniga, Cornelia Eckert, Geertruy Te Kronnie, Jean-Pierre Bourquin, Beat Bornhauser, Rolf Koehler, Claus R Bartram, Wolf-Dieter Ludwig, Kirsten Bleckmann, Stefanie Groeneveld-Krentz, Denis Schewe, Stefanie V Junk, Laura Hinze, Norman Klein, Christian P Kratz, Andrea Biondi, Arndt Borkhardt, Andreas Kulozik, Martina U Muckenthaler, Giuseppe Basso, Maria Grazia Valsecchi, Shai Izraeli, Britt-Sabina Petersen, Andre Franke, Petra Dörge, Doris Steinemann, Oskar A Haas, Renate Panzer-Grümayer, Hélène Cavé, Richard S Houlston, Gunnar Cario, Martin Schrappe, Martin Zimmermann
Purpose Somatic deletions that affect the lymphoid transcription factor-coding gene IKZF1 have previously been reported as independently associated with a poor prognosis in pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). We have now refined the prognostic strength of IKZF1 deletions by analyzing the effect of co-occurring deletions. Patients and Methods The analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica-Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22...
April 20, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29490943/loss-of-pax5-exploits-sca1-bcr-ablp190-susceptibility-to-confer-the-metabolic-shift-essential-for-pb-all
#16
Alberto Martín-Lorenzo, Franziska Auer, Lai N Chan, Idoia García-Ramírez, Ines Gonzalez-Herrero, Guillermo Rodríguez-Hernández, Christoph Bartenhagen, Martin Dugas, Michael Gombert, Sebastian Ginzel, Oscar Blanco, Alberto Orfao, Diego Alonso-López, Javier De Las Rivas, Maria Begoña García-Cenador, Francisco Javier García Criado, Markus Müschen, Isidro Sánchez-García, Arndt Borkhardt, Carolina Vicente-Dueñas, Julia Hauer
Preleukemic clones carrying BCR-ABLp190 oncogenic lesions are found in neonatal cord blood, where the majority of preleukemic carriers do not convert into precursor B-cell acute lymphoblastic leukemia (pB-ALL). However, the critical question of how these preleukemic cells transform into pB-ALL remains undefined. Here we model a BCR-ABLp190 preleukemic state and show that limiting BCR-ABLp190 expression to hematopoietic stem/progenitor cells (HS/PC) in mice (Sca1-BCR-ABLp190) causes pB-ALL at low penetrance, which resembles the human disease...
February 28, 2018: Cancer Research
https://www.readbyqxmd.com/read/29475930/primary-gastric-ebv-positive-diffuse-large-b-cell-lymphoma-dlbcl-of-the-elderly-with-plasmablastic-differentiation
#17
Ming Hu, Jose Trevino, Lijun Yang, Dengfeng Cao, Xiuli Liu, Jinping Lai
Epstein-Barr virus (EBV)-positive diffuse large B cell lymphoma (DLBCL) of the elderly is a rare subtype of B-cell neoplasms. Primary gastric EBV-positive DLBCL of the elderly with partial plasmablastic phenotype is extremely rare. Differentiation of EBV-positive DLBCL of the elderly with partial plasmablastic phenotype from true plasmablastic lymphoma (PBL) is difficult and very important from the therapeutic and prognostic point of view. Here we report a case of a 59-year-old man with upper gastrointestinal bleeding...
March 2018: In Vivo
https://www.readbyqxmd.com/read/29467311/epstein-barr-virus-nuclear-antigen-leader-protein-coactivates-ep300
#18
Chong Wang, Hufeng Zhou, Yong Xue, Jun Liang, Yohei Narita, Catherine Gerdt, Amy Y Zheng, Runsheng Jiang, Stephen Trudeau, Chih-Wen Peng, Benjamin E Gewurz, Bo Zhao
Epstein-Barr virus nuclear antigen (EBNA) leader protein (EBNALP) is one of the first viral genes expressed upon B-cell infection. EBNALP is essential for EBV-mediated B-cell immortalization. EBNALP is thought to function primarily by coactivating EBNA2-mediated transcription. Chromatin immune precipitation followed by deep sequencing (ChIP-seq) studies highlight that EBNALP frequently cooccupies DNA sites with host cell transcription factors (TFs), in particular, EP300, implicating a broader role in transcription regulation...
May 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29453973/pax5-haploinsufficiency-induce-cancer-cell-dormancy-in-raji-cells
#19
Xue Liang, Jia Gu, TongJuan Li, Lei Zhao, Xing Fu, Wei Zhang, Jue Wang, Zhen Shang, Wei Huang, Jianfeng Zhou
PAX5 mutations have important role in leukemogenesis and leukemia relapse, cancer cell dormancy participates in cancer relapse, but there was no report about PAX5 mutation inducing cancer cell dormancy. we constructed the PAX5 deletion Raji cell lines using gene editing technology, evaluated dormancy biological characteristics of cell lines. Our results showed PAX5 haploinsufficiency restrained the proliferation of Raji cells, induced G0/G1 arrest of Raji cells, reduced chemotherapy sensitivity. The tumor formation rate reduced in PAX5 mutation Raji cells...
June 1, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29430664/blimp-1-is-insufficient-to-induce-antibody-secretion-in-the-absence-of-irf4-in-dt40-cells
#20
P M Budzyńska, M K Kyläniemi, O Lassila, K-P Nera, J Alinikula
Differentiation of B cells into antibody-secreting cells (ASCs), plasmablasts and plasma cells is regulated by a network of transcription factors. Within this network, factors including PAX5 and BCL6 prevent ASC differentiation and maintain the B cell phenotype. In contrast, BLIMP-1 and high IRF4 expression promote plasma cell differentiation. BLIMP-1 is thought to induce immunoglobulin secretion, whereas IRF4 is needed for the survival of ASCs. The role of IRF4 in the regulation of antibody secretion has remained controversial...
March 2018: Scandinavian Journal of Immunology
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