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https://www.readbyqxmd.com/read/27913604/conversion-of-t-cells-to-b-cells-by-inactivation-of-polycomb-mediated-epigenetic-suppression-of-the-b-lineage-program
#1
Tomokatsu Ikawa, Kyoko Masuda, Takaho A Endo, Mitsuhiro Endo, Kyoichi Isono, Yoko Koseki, Rinako Nakagawa, Kohei Kometani, Junichiro Takano, Yasutoshi Agata, Yoshimoto Katsura, Tomohiro Kurosaki, Miguel Vidal, Haruhiko Koseki, Hiroshi Kawamoto
In general, cell fate is determined primarily by transcription factors, followed by epigenetic mechanisms fixing the status. While the importance of transcription factors controlling cell fate has been well characterized, epigenetic regulation of cell fate maintenance remains to be elucidated. Here we provide an obvious fate conversion case, in which the inactivation of polycomb-medicated epigenetic regulation results in conversion of T-lineage progenitors to the B-cell fate. In T-cell-specific Ring1A/B-deficient mice, T-cell development was severely blocked at an immature stage...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913602/clonal-conversion-of-b-lymphoid-leukemia-reveals-cross-lineage-transfer-of-malignant-states
#2
Rajesh Somasundaram, Josefine Åhsberg, Kazuki Okuyama, Jonas Ungerbäck, Henrik Lilljebjörn, Thoas Fioretos, Tobias Strid, Mikael Sigvardsson
Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913495/germ-line-mutations-associated-with-leukemias
#3
Christopher C Porter
Several genetic syndromes have long been associated with a predisposition to the development of leukemia, including bone marrow failure syndromes, Down syndrome, and Li Fraumeni syndrome. Recent work has better defined the leukemia risk and outcomes in these syndromes. Also, in the last several years, a number of other germ line mutations have been discovered to define new leukemia predisposition syndromes, including ANKRD26, GATA2, PAX5, ETV6, and DDX41 In addition, data suggest that a substantial proportion of patients with therapy related leukemias harbor germ line mutations in DNA damage response genes such as BRCA1/2 and TP53 Recognition of clinical associations, acquisition of a thorough family history, and high index-of-suspicion are critical in the diagnosis of these leukemia predisposition syndromes...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911806/permissive-roles-of-cytokines-interleukin-7-and-flt3-ligand-in-mouse-b-cell-lineage-commitment
#4
Lilly von Muenchow, Llucia Alberti-Servera, Fabian Klein, Giuseppina Capoferri, Daniela Finke, Rhodri Ceredig, Antonius Rolink, Panagiotis Tsapogas
Hematopoietic cells are continuously generated throughout life from hematopoietic stem cells, thus making hematopoiesis a favorable system to study developmental cell lineage commitment. The main factors incorporating environmental signals to developing hematopoietic cells are cytokines, which regulate commitment of hematopoietic progenitors to the different blood lineages by acting either in an instructive or a permissive manner. Fms-like tyrosine kinase-3 (Flt3) ligand (FL) and Interleukin-7 (IL-7) are cytokines pivotal for B-cell development, as manifested by the severely compromised B-cell development in their absence...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27888664/ebv-associated-but-hhv8-unrelated-double-hit-effusion-based-lymphoma
#5
Bo-Jung Chen, David Yen-Ting Chen, Chun-Chi Kuo, Shih-Sung Chuang
Effusion-based lymphoma is a rare and unique type of large B-cell lymphoma presenting in effusion without a mass lesion. It shares many clinicopathological features with primary effusion lymphoma (PEL), but is distinct from PEL by the absence of HHV8 association. Double hit lymphoma (DHL) is an aggressive B-cell lymphoma, defined by concurrent rearrangement of MYC and BCL2 or BCL6. DHL often presents as lymphadenopathy or an extranodal mass, but rarely occurs in effusion. Here we report a 61-year-old male with alcoholic cirrhosis presenting as massive ascites and left pleural effusion...
November 26, 2016: Diagnostic Cytopathology
https://www.readbyqxmd.com/read/27870151/ph-like-acute-lymphoblastic-leukemia-with-a-novel-pax5-kidins220-fusion-transcript
#6
Kenichi Sakamoto, Toshihiko Imamura, Takuyo Kanayama, Mio Yano, Daisuke Asai, Takao Deguchi, Yoshiko Hashii, Akihiko Tanizawa, Yusei Ohshima, Nobutaka Kiyokawa, Keizo Horibe, Atsushi Sato
Although "paired box 5" (PAX5)-related fusion genes are well documented in childhood B-cell precursor acute lymphoblastic leukemia (ALL), these types of fusion with the exception of PAX5-JAK2 are rarely seen in patients with gene expression profiles similar to those of BCR-ABL1 (Philadelphia)-positive ALL (Ph-like ALL). We report a novel fusion of the genes PAX5 and "kinase D-interacting substrate of 220 kDa" (KIDINS220, also known as ARMS) in a Ph-like ALL. As PAX5 is a master regulator of B-lymphocyte differentiation, PAX5 rearrangements induce a differentiation block in B lymphocytes...
November 7, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27835756/regulated-localization-of-an-aid-complex-with-e2a-pax5-and-irf4-at-the-igh-locus
#7
Jannek Hauser, Christine Grundström, Ramesh Kumar, Thomas Grundström
Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates somatic hypermutation (SH) and class switch recombination (CSR) by deaminating cytosine to uracil. The targeting of AID and therefore SH and CSR to Ig genes is a central process of the immune system, but the trans-acting factors mediating the specific targeting have remained elusive. Here we show that defective calmodulin inhibition of the transcription factor E2A after activation of the B cell receptor (BCR) leads to reduced BCR, IL4 plus CD40 ligand stimulated CSR to IgE and instead CSR to other Ig classes...
November 8, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27829444/potential-molecular-characteristics-in-situ-in-response-to-repetitive-uvb-irradiation
#8
Wenqi Chen, Jinhai Zhang
BACKGROUND: To identify molecular characteristics in situ in response to repetitive UVB (ultraviolet-B) irradiation. METHODS: Microarray data from the Gene Expression Omnibus were re-analyzed to identify DEGs (differentially expressed genes) between UVB-irradiated and non-irradiated skin biopsies. Enrichment and annotation analyses were performed respectively using DAVID, and TSGene and TAG databases. PPIs (protein-protein interactions) were analyzed using STRING, and miRNAs (microRNAs) and TFs (transcription factors) were predicted separately by miRNA-related databases and ENCODE...
November 10, 2016: Diagnostic Pathology
https://www.readbyqxmd.com/read/27819178/myelodysplastic-syndromes-and-acute-leukemia-with-genetic-predispositions-a-new-challenge-for-hematologists
#9
Nicolas Duployez, Sophie Lejeune, Aline Renneville, Claude Preudhomme
The determination of an underlying genetic predisposition is not automatically part of the diagnosis of hematological malignancies (HM) in routine practice. However, it is assumed that genetic predispositions to HM are currently underestimated due to great variations in disease phenotype, variable latency and incomplete penetrance. Most of patients do not display any biological or clinical signs besides the overt hematological disease and many of them have a lack of personal or family history of malignancies...
December 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27802200/modern-molecular-biomarkers-of-head-and-neck-cancer-part-i-epigenetic-diagnostics-and-prognostics-systematic-review
#10
Gintaras Juodzbalys, David Kasradze, Marco Cicciù, Aurimas Sudeikis, Laurynas Banys, Pablo Galindo-Moreno, Zygimantas Guobis
INTRODUCTION: Nearly half of the head and neck cancer cases are diagnosed in late stages. Traditional screening modalities have many disadvantages. The aim of the present article was to review the scientific literature about novel head and neck cancer diagnostics - epigenetic biomarkers. EVIDENCE ACQUISITION: A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database. Authors conducted the search of articles in English language published from 2004 to 2015...
September 30, 2016: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27795542/genetic-and-epigenetic-aberrations-of-pediatric-leukemia-and-clinical-applications
#11
Junko Takita
Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Although fusion genes generated by chromosomal rearrangements are the most frequent genetic alterations in pediatric ALL, fusions are insufficient for the development of this disease, and thus, cannot serve as therapeutic targets for ALL. Recently, integrated genetic analysis using next generation sequencing technology has revealed the genetic landscapes of pediatric ALL. These studies disclosed that in addition to fusion genes, aberrations of cell proliferation pathways and epigenetic regulations are also involved in the pathogenesis of pediatric ALL...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27756164/biallelic-loss-of-cdkn2a-is-associated-with-poor-response-to-treatment-in-pediatric-acute-lymphoblastic-leukemia
#12
Marcin Braun, Agata Pastorczak, Wojciech Fendler, Joanna Madzio, Bartlomiej Tomasik, Joanna Taha, Marta Bielska, Lukasz Sedek, Tomasz Szczepanski, Michal Matysiak, Katarzyna Derwich, Monika Lejman, Jerzy Kowalczyk, Bernarda Kazanowska, Wanda Badowska, Jan Styczynski, Nina Irga-Jaworska, Joanna Trelinska, Beata Zalewska-Szewczyk, Filip Pierlejewski, Iwona Wlodarska, Wojciech Młynarski
The inactivation of tumor suppressor genes located within 9p21 locus (CDKN2A, CDKN2B) occurs in up to 30% of children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but its independent prognostic significance remains controversial. In order to investigate the prognostic impact of deletions and promoter methylation within 9p21, 641 children with newly diagnosed BCP-ALL using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) were investigated. A total of 169 (26.4%) microdeletions in 9p21 were detected, of which 71 were homozygous...
October 18, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27748274/level-of-pax5-in-differential-diagnosis-of-non-hodgkin-s-lymphoma
#13
Brij Bharti, Sachin Shukla, Ratnakar Tripathi, Suman Mishra, Mohan Kumar, Manoj Pandey, Rajnikant Mishra
BACKGROUND & OBJECTIVES: The PAX5, a paired box transcription factor and B-cell activator protein (BSAP), activates B-cell commitment genes and represses non-B-cell lineage genes. About 14 transcript variants of PAX5 have been observed in human. Any alteration in its expression pattern leads to lymphogenesis or associated diseases and carcinogenesis in non-lymphoid tissues. Its mechanisms of function in pathophysiology of non-Hodgkin's lymphoma (NHL) are unclear. This study was intended to explore influence of PAX5 in cascade of NHL pathogenesis and diagnosis...
May 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/27740969/alk-positive-large-b-cell-lymphoma-a-clinicopathologic-study-of-26-cases-with-review-of-additional-108-cases-in-the-literature
#14
Zenggang Pan, Shimin Hu, Min Li, Yi Zhou, Young S Kim, Vishnu Reddy, Jennifer N Sanmann, Lynette M Smith, Mingyi Chen, Zifen Gao, Huan-You Wang, Ji Yuan
Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK LBCL) is a rare, aggressive subtype of diffuse large B-cell lymphoma with characteristic ALK rearrangements. Diagnosis of ALK LBCL can be challenging because of its rarity, unique morphologic characteristics, and unusual immunophenotypic features, which significantly overlap with other hematologic and nonhematologic neoplasms. The purpose of this study is to further explore the clinicopathologic features of ALK LBCL to ensure the awareness and accurate diagnosis of this entity...
October 12, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27729548/systemic-delivery-of-bone-marrow-mesenchymal-stem-cells-for-in-situ-intervertebral-disc-regeneration
#15
Carla Cunha, Catarina R Almeida, Maria Inês Almeida, Andreia M Silva, Maria Molinos, Sofia Lamas, Catarina L Pereira, Graciosa Q Teixeira, António T Monteiro, Susana G Santos, Raquel M Gonçalves, Mário A Barbosa
: : Cell therapies for intervertebral disc (IVD) regeneration presently rely on transplantation of IVD cells or stem cells directly to the lesion site. Still, the harsh IVD environment, with low irrigation and high mechanical stress, challenges cell administration and survival. In this study, we addressed systemic transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs) intravenously into a rat IVD lesion model, exploring tissue regeneration via cell signaling to the lesion site...
October 11, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27664237/superenhancer-reprogramming-drives-a-b-cell-epithelial-transition-and-high-risk-leukemia
#16
Yeguang Hu, Zhihong Zhang, Mariko Kashiwagi, Toshimi Yoshida, Ila Joshi, Nilamani Jena, Rajesh Somasundaram, Akinola Olumide Emmanuel, Mikael Sigvardsson, Julien Fitamant, Nabeel El-Bardeesy, Fotini Gounari, Richard A Van Etten, Katia Georgopoulos
IKAROS is required for the differentiation of highly proliferative pre-B-cell precursors, and loss of IKAROS function indicates poor prognosis in precursor B-cell acute lymphoblastic leukemia (B-ALL). Here we show that IKAROS regulates this developmental stage by positive and negative regulation of superenhancers with distinct lineage affiliations. IKAROS defines superenhancers at pre-B-cell differentiation genes together with B-cell master regulators such as PAX5, EBF1, and IRF4 but is required for a highly permissive chromatin environment, a function that cannot be compensated for by the other transcription factors...
September 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27623204/expression-of-sox11-pax5-ttf-1-and-isl-1-in-medulloblastoma
#17
Piotr Czapiewski, Adam Gorczynski, Klaudia Radecka, Claudia Wiewiora, Johannes Haybaeck, Patrick Adam, Falko Fend, Magdalena Zakrzewska, Krzysztof Zakrzewski, Pawel P Liberski, Wojciech Biernat
: The aim of our study was to evaluate the immunohistochemical expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma (MB) to investigate their diagnostic usefulness. METHODS: Immunohistochemical expression of PAX5 (two antibodies: Dako, DAK-Pax5; and BD, clone 24), TTF-1 (Dako, 8G7G3/1), SOX11 (CL0142; Abcam) and ISL-1 (1 H9, Abcam) was analyzed using the h-score and Remmele score in 25 cases of MB. RESULTS: There were 18 MBs of classic and 7 of desmoplastic type...
November 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27611742/novel-bcr-abl1-fusion-and-leukemic-mutations-of-setbp1-pax5-and-tp53-detected-by-next-generation-sequencing-in-chronic-myeloid-leukemia
#18
Shuang Fu, Yanping Hu, Yu Fu, Fang Chen, Xuan Liu, Minyu Zhang, Xiaohui Wang, Shichun Tu, Jihong Zhang
Patients with BCR-ABL1 fusion genes are potential candidates for targeted therapy with tyrosine kinase inhibitor (TKI) imatinib. However, novel BCR-ABL1 fusion variants can be undetected by qRT-PCR-based routine molecular screening, affecting immediate patient management and proper treatment selection. In this study, we describe a case of chronic myeloid leukemia (CML) harboring a novel BCR-ABL1 variant gene. Although Fluorescent In situ Hybridization (FISH) analysis suggested Philadelphia (Ph) translocation, qRT-PCR screening failed to detect the presence of a functional fusion transcript, which is critical for selecting targeted therapy against BCR-ABL1 fusion with aberrant kinase activity...
August 12, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27572852/identification-of-hub-genes-and-regulatory-factors-of-glioblastoma-multiforme-subgroups-by-rna-seq-data-analysis
#19
Yanan Li, Weijie Min, Mengmeng Li, Guosheng Han, Dongwei Dai, Lei Zhang, Xin Chen, Xinglai Wang, Yuhui Zhang, Zhijian Yue, Jianmin Liu
Glioblastoma multiforme (GBM) is the most common malignant brain tumor. This study aimed to identify the hub genes and regulatory factors of GBM subgroups by RNA sequencing (RNA-seq) data analysis, in order to explore the possible mechanisms responsbile for the progression of GBM. The dataset RNASeqV2 was downloaded by TCGA-Assembler, containing 169 GBM and 5 normal samples. Gene expression was calculated by the reads per kilobase per million reads measurement, and nor malized with tag count comparison...
October 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27549353/evaluation-of-pax5-expression-and-comparison-with-bla-36-and-cd79%C3%AE-cy-in-feline-non-hodgkin-lymphoma
#20
R Felisberto, J Matos, M Alves, J Cabeçadas, J Henriques
Paired box gene 5 (Pax5) is a widely used B-cell marker for human and canine non-Hodgkin's lymphoma (nHL); however, in the literature there is only one case report using Pax5 in a cat B-cell lymphoma. The purposes of this study were to investigate the expression and detection of B-cell specific activator protein (BSAP) using a monoclonal anti-Pax5 antibody in feline nHL (FnHL) tissue samples to evaluate its diagnostic relevance as a B-cell marker. A total of 45 FnHL samples in 45 cats were evaluated. B-cell lymphoma was the most common immunophenotype (51...
August 22, 2016: Veterinary and Comparative Oncology
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