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https://www.readbyqxmd.com/read/28096536/germline-ikaros-mutation-associated-with-primary-immunodeficiency-that-progressed-to-t-cell-acute-lymphoblastic-leukemia
#1
N Yoshida, H Sakaguchi, H Muramatsu, Y Okuno, C Song, S Dovat, A Shimada, M Ozeki, H Ohnishi, T Teramoto, T Fukao, N Kondo, Y Takahashi, K Matsumoto, K Kato, S Kojima
Leukemia accepted article preview online, 18 January 2017. doi:10.1038/leu.2017.25.
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074872/corrigendum-targeting-high-dynamin-2-dnm2-expression-by-restoring-ikaros-function-in-acute-lymphoblastic-leukemia
#2
Zheng Ge, Yan Gu, Qi Han, Gang Zhao, Min Li, Jianyong Li, Baoan Chen, Tianyu Sun, Sinisa Dovat, Robert Peter Gale, Chunhua Song
No abstract text is available yet for this article.
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28052520/ikaros-expression-in-distinct-bone-marrow-cell-populations-as-a-candidate-biomarker-for-outcome-with-lenalidomide-dexamethasone-therapy-in-multiple-myeloma
#3
Arnold Bolomsky, Wolfgang Hübl, Stefano Spada, Ercan Müldür, Karin Schlangen, Daniel Heintel, Alberto Rocci, Adalbert Weißmann, Veronique Fritz, Martin Willheim, Niklas Zojer, Antonio Palumbo, Heinz Ludwig
Immunomodulatory drugs (IMiDs) are a cornerstone in the treatment of multiple myeloma (MM), but specific markers to predict outcome are still missing. Recent work pointed to a prognostic role for IMiD target genes (e.g. CRBN). Moreover, indirect activity of IMiDs on immune cells correlated with outcome, raising the possibility that cell populations in the bone marrow (BM) microenvironment could serve as biomarkers. We therefore analysed gene expression levels of six IMiD target genes in whole BM samples of 44 myeloma patients treated with lenalidomide-dexamethasone...
January 4, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28038358/il-22-promotes-fas-expression-in-oligodendrocytes-and-inhibits-foxp3-expression-in-t-cells-by-activating-the-nf-%C3%AE%C2%BAb-pathway-in-multiple-sclerosis
#4
Jin Zhen, Jun Yuan, Yongwang Fu, Runxiu Zhu, Meiling Wang, Hong Chang, Yan Zhao, Dong Wang, Zuneng Lu
Multiple sclerosis (MS) is characterized by an increase in interleukin-22 and Fas, and a decrease in FOXP3, among other factors. In this study, we examined patients with MS and healthy control subjects and used the experimental autoimmune encephalomyelitis (EAE) animal model to identify the effects of IL-22 on oligodendrocytes and T cells in MS development. In MS, the expression of Fas in oligodendrocytes and IL-22 in CD4(+)CCR4(+)CCR6(+)CCR10(+) T cells was enhanced. Ikaros and FOXP3 were both decreased in T cells...
December 27, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/28030830/ikaros-regulation-of-the-bcl6-bach2-axis-and-its-clinical-relevance-in-acute-lymphoblastic-leukemia
#5
Zheng Ge, Xilian Zhou, Yan Gu, Qi Han, Jianyong Li, Baoan Chen, Qinyu Ge, Elanora Dovat, Jonathon L Payne, Tianyu Sun, Chunhua Song, Sinisa Dovat
B-Cell CLL/Lymphoma 6 (BCL6) is a proto-oncogene that is highly expressed in acute lymphoblastic leukemia (ALL). BTB and CNC Homology 1 Basic Leucine Zipper Transcription Factor 2 (BACH2) is a suppressor of transcription. The BACH2-BCL6 balance controls selection at the pre-B cell receptor checkpoint by regulating p53 expression. However, the underlying mechanism and the clinical relevance of the BCL6/BACH2 axis are unknown. Here, we found that Ikaros, a tumor suppressor encoded by IKZF1, directly binds to both the BCL6 and BACH2 promoters where it suppresses BCL6 and promotes BACH2 expression in B-cell ALL (B-ALL) cells...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/28017969/ikzf1-expression-is-a-prognostic-marker-in-newly-diagnosed-standard-risk-multiple-myeloma-treated-with-lenalidomide-and-intensive-chemotherapy-a-study-of-the-german-myeloma-study-group-dsmm
#6
J Krönke, F Kuchenbauer, M Kull, V Teleanu, L Bullinger, D Bunjes, A Greiner, S Kolmus, S Köpff, M Schreder, L-O Mügge, C Straka, M Engelhardt, H Döhner, H Einsele, F Bassermann, R Bargou, S Knop, C Langer
Lenalidomide is an immunomodulatory compound with high clinical activity in multiple myeloma. Lenalidomide binding to the Cereblon (CRBN) E3 ubiquitin ligase results in targeted ubiquitination and degradation of the lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) leading to growth-inhibition of multiple myeloma cells. Recently, Basigin (BSG) was identified as another protein regulated by CRBN that is involved in the activity of lenalidomide. Here, we analyzed the prognostic value of IKZF1, IKZF3, CRBN and BSG mRNA expression levels in pretreatment plasma cells from sixty patients with newly diagnosed multiple myeloma uniformly treated with lenalidomide in combination with intensive chemotherapy within a clinical trial...
December 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28001429/single-crystalline-hexagonal-silicon-germanium
#7
Håkon Ikaros T Hauge, Sonia Conesa-Boj, Marcel A Verheijen, Sebastian Koelling, Erik P A M Bakkers
Group IV materials with the hexagonal diamond crystal structure have been predicted to exhibit promising optical and electronic properties. In particular, hexagonal silicon-germanium (Si1-xGex) should be characterized by a tunable direct band gap with implications ranging from Si-based light-emitting diodes to lasers and quantum dots for single photon emitters. Here we demonstrate the feasibility of high-quality defect-free and wafer-scale hexagonal Si1-xGex growth with precise control of the alloy composition and layer thickness...
December 27, 2016: Nano Letters
https://www.readbyqxmd.com/read/27994173/transgenic-overexpression-of-baff-regulates-the-expression-of-immune-related-genes-in-zebrafish-danio-rerio
#8
Li Zhang, Chao Liu, Xin Zhou, Ying Xie, Libo Su, Qi Geng, Binghui Liu, Shufeng Liu
The B-cell activating factor (BAFF) is a member of tumour necrosis factor (TNF) superfamily that specifically regulates B lymphocyte proliferation and survival. Excess BAFF leads to overproduction of antibodies for secretion, anti-dsDNA antibodies and a lupus-like syndrome in mice. To investigate whether transgenic overexpression of the zebrafish BAFF leads to immunoglobulin changes and/or early maturing of the immune system, a Tol2-GFP-2A-BAFF/His recombinant plasmid was constructed by inserting a 2A peptide between the green fluorescent protein (GFP) and BAFF sequences...
December 2016: Journal of Genetics
https://www.readbyqxmd.com/read/27993894/downregulation-of-azgp1-by-ikaros-and-histone-deacetylase-promotes-tumor-progression-through-the-pten-akt-and-cd44s-pathways-in-hepatocellular-carcinoma
#9
Hua Tian, Chao Ge, Fangyu Zhao, Miaoxin Zhu, Lin Zhang, Qi Huo, Hong Li, Taoyang Chen, Haiyang Xie, Ying Cui, Ming Yao, Jinjun Li
Increasing evidence has shown that zinc-alpha2-glycoprotein (AZGP1) is associated with the progression and prognosis of several tumor types. However, little is known regarding the underlying molecular mechanisms of AZGP1 in hepatocellular carcinoma (HCC). In this study, we report that transcription factor Ikaros bound to the AZGP1 promoter and increased its expression in HCC cells. The downregulation of AZGP1 was associated with histone deacetylation in HCC. In addition, the positive feedback regulation via acetylation of histone H4-mediated transactivation of the Ikaros promoter and the Ikaros-mediated transactivation of the acetylation of histone H4 were crucial for regulating AZGP1 expression in HCC cells...
December 17, 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27992025/construction-and-validation-of-a-tool-to-assess-the-use-of-light-technologies-at-intensive-care-units
#10
Pabliane Matias Lordelo Marinho, Maria Pontes de Aguiar Campos, Eliana Ofélia Llapa Rodrigues, Cristiane Franca Lisboa Gois, Ikaro Daniel de Carvalho Barreto
Objective: to construct and validate a tool to assess the use of light technologies by the nursing team at Intensive Care Units. Method: methodological study in which the tool was elaborated by means of the psychometric method for construction based on the categorization of health technologies by Merhy and Franco, from the National Humanization Policy, using the Nursing Intervention Classification taxonomy to categorize the domains of the tool. Agreement Percentages and Content Validity Indices were used for the purpose of validation...
December 19, 2016: Revista Latino-americana de Enfermagem
https://www.readbyqxmd.com/read/27979924/tumor-suppressors-btg1-and-ikzf1-cooperate-during-mouse-leukemia-development-and-increase-relapse-risk-in-b-cell-precursor-acute-lymphoblastic-leukemia-patients
#11
Blanca Scheijen, Judith M Boer, Rene' Marke, Esther Tijchon, Dorette van Ingen Schenau, Esme' Waanders, Liesbeth van Emst, Laurens T van der Meer, Rob Pieters, Gabriele Escherich, Martin A Horstmann, Edwin Sonneveld, Nicola Venn, Rosemary Sutton, Luciano Dalla-Pozza, Roland P Kuiper, Peter M Hoogerbrugge, Monique L den Boer, Frank N van Leeuwen
Deletions and mutations affecting lymphoid transcription factor IKZF1 (IKAROS) are associated with an increased relapse risk and poor outcome in B-cell precursor acute lymphoblastic leukemia. However, additional genetic events may either enhance or negate the effects of IKZF1 deletions on prognosis. In a large discovery cohort of 533 childhood B-cell precursor acute lymphoblastic leukemia patients, we observed that single copy losses of BTG1 were significantly enriched in IKZF1-deleted B-cell precursor acute lymphoblastic leukemia (P=0...
December 15, 2016: Haematologica
https://www.readbyqxmd.com/read/27939403/abnormal-hematopoiesis-and-autoimmunity-in-human-subjects-with-germline-ikzf1-mutations
#12
Akihiro Hoshino, Satoshi Okada, Kenichi Yoshida, Naonori Nishida, Yusuke Okuno, Hiroo Ueno, Motoi Yamashita, Tsubasa Okano, Miyuki Tsumura, Shiho Nishimura, Sonoko Sakata, Masao Kobayashi, Haruna Nakamura, Junji Kamizono, Kanako Mitsui-Sekinaka, Takuya Ichimura, Shouichi Ohga, Yozo Nakazawa, Masatoshi Takagi, Kohsuke Imai, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Seiji Kojima, Shigeaki Nonoyama, Tomohiro Morio, Hirokazu Kanegane
BACKGROUND: Ikaros, which is encoded by IKZF1, is a transcriptional factor that play a critical role in hematopoiesis. Somatic IKZF1 alterations are known to be involved in the pathogenesis of leukemia in human subjects. Recently, immunodeficiency caused by germline IKZF1 mutation has been described. OBJECTIVE: We sought to describe the clinical and immunologic phenotypes of Japanese patients with heterozygous IKZF1 mutations. METHODS: We performed whole-exome sequencing in patients from a dysgammaglobulinemia or autoimmune disease cohort and used a candidate gene approach in 4 patients...
December 1, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27899802/genomic-and-transcriptional-landscape-of-p2ry8-crlf2-positive-childhood-acute-lymphoblastic-leukemia
#13
C Vesely, C Frech, C Eckert, G Cario, A Mecklenbräuker, U Zur Stadt, K Nebral, F Kraler, S Fischer, A Attarbaschi, M Schuster, C Bock, H Cavé, A von Stackelberg, M Schrappe, M A Horstmann, G Mann, O A Haas, R Panzer-Grümayer
Children with P2RY8-CRLF2-positive ALL have an increased relapse risk. Their mutational and transcriptional landscape as well as the respective patterns at relapse remains largely elusive. We therefore performed an integrated analysis of whole-exome and RNA-sequencing in 41 major clone fusion-positive cases including 19 matched diagnosis/relapse pairs. We detected a variety of frequently subclonal and highly instable JAK/STAT but also RTK/Ras pathway activating mutations in 76% of cases at diagnosis and virtually all relapses...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890933/preclinical-activity-of-cpi-0610-a-novel-small-molecule-bromodomain-and-extra-terminal-protein-inhibitor-in-the-therapy-of-multiple-myeloma
#14
K T Siu, J Ramachandran, A J Yee, H Eda, L Santo, C Panaroni, J A Mertz, R J Sims Iii, M R Cooper, N Raje
Inhibition of the bromodomain and extra-terminal (BET) proteins is a promising therapeutic strategy for various hematologic cancers. Previous studies suggest that BET inhibitors constrain tumor cell proliferation and survival mainly through the suppression of MYC transcription and activity. However, suppression of the transcription of additional genes also contributes to the antitumor activity of BET inhibitors but is less well understood. Here we examined the therapeutic potential of CPI-0610, a potent BET inhibitor currently undergoing phase I clinical testing, in multiple myeloma (MM)...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27885263/targeting-high-dynamin-2-dnm2-expression-by-restoring-ikaros-function-in-acute-lymphoblastic-leukemia
#15
Zheng Ge, Yan Gu, Qi Han, Gang Zhao, Min Li, Jianyong Li, Baoan Chen, Tianyu Sun, Sinisa Dovat, Robert Peter Gale, Chunhua Song
Dynamin-2 (DNM2) is a GTPase essential for intracellular vesicle formation and trafficking, cytokinesis and receptor endocytosis. Mutations in DNM2 are common in early T-cell precursor acute lymphoblastic leukemia. However, DNM2 expression in other types of ALL are not reported. We studied DNM2 mRNA level in adults with B- and T-cell ALL. We found DNM2 is more highly expressed compared with normals in both forms of ALL. High DNM2 expression is associated with some clinical and laboratory features, inferior outcomes and with leukaemia cell proliferation...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27869105/an-open-access-database-for-the-evaluation-of-heart-sound-algorithms
#16
Chengyu Liu, David Springer, Qiao Li, Benjamin Moody, Ricardo Abad Juan, Francisco J Chorro, Francisco Castells, José Millet Roig, Ikaro Silva, Alistair E W Johnson, Zeeshan Syed, Samuel E Schmidt, Chrysa D Papadaniil, Leontios Hadjileontiadis, Hosein Naseri, Ali Moukadem, Alain Dieterlen, Christian Brandt, Hong Tang, Maryam Samieinasab, Mohammad Reza Samieinasab, Reza Sameni, Roger G Mark, Gari D Clifford
In the past few decades, analysis of heart sound signals (i.e. the phonocardiogram or PCG), especially for automated heart sound segmentation and classification, has been widely studied and has been reported to have the potential value to detect pathology accurately in clinical applications. However, comparative analyses of algorithms in the literature have been hindered by the lack of high-quality, rigorously validated, and standardized open databases of heart sound recordings. This paper describes a public heart sound database, assembled for an international competition, the PhysioNet/Computing in Cardiology (CinC) Challenge 2016...
December 2016: Physiological Measurement
https://www.readbyqxmd.com/read/27865806/ikaros-exploiting-and-targeting-the-hematopoietic-stem-cell-niche-in%C3%A2-b-progenitor-acute-lymphoblastic-leukemia
#17
REVIEW
Michelle L Churchman, Charles G Mullighan
Genetic alterations of IKZF1 encoding the lymphoid transcription factor IKAROS are a hallmark of high-risk B-progenitor acute lymphoblastic leukemia (ALL), such as BCR-ABL1-positive (Ph+) and Ph-like ALL, and are associated with poor outcome even in the era of contemporary chemotherapy incorporating tyrosine kinase inhibitors. Recent experimental mouse modeling of B-progenitor ALL has shown that IKZF1 alterations have multiple effects, including arresting differentiation, skewing lineage of leukemia from myeloid to lymphoid, and, in Ph+ leukemia, conferring resistance to tyrosine kinase inhibitor (TKI) therapy without abrogating ABL1 inhibition...
February 2017: Experimental Hematology
https://www.readbyqxmd.com/read/27849215/communication-self-assessment-by-public-prosecutors-in-a-north-eastern-brazilian-state
#18
Neuza Josina Sales, Daniel Francisco Neyra Castaneda, Íkaro Daniel de Carvalho Barreto, Marina Paoliello, Silvia Márcia Andrade Campanha
Purpose: To describe how public prosecutors self-assess their communication approaches and how listeners react to them; to analyze how this relates to gender, age, and work experience. Methods: Descriptive, transversal study. A questionnaire was developed and sent to 126 public prosecutors for completion. Thirty-three completed questionnaires were sent back. The independent variables were gender, age, and number of years of professional experience. The dependent variables were communication self-assessment throughout the years of work, communication parameters used, and listeners' reactions...
November 2016: CoDAS
https://www.readbyqxmd.com/read/27826566/variations-in-mrna-and-protein-levels-of-ikaros-family-members-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#19
Julie L Mitchell, Thomas M Yankee
BACKGROUND: Pediatric T cell acute lymphoblastic leukemia (T-ALL) is a highly heterogeneous disease in which the cells share phenotypic characteristics with normal human thymocytes. The Ikaros family of transcription factors includes five members that are required for normal T cell development and are implicated in leukemogenesis. The goal of this work was to correlate the pattern of expression of Ikaros family members with the phenotype of the T-ALL cells. METHODS: We obtained twenty-four samples from pediatric T-ALL patients and used multi-parameter flow cytometry to characterize each sample, comparing the phenotype of the leukemic cells with normal human thymocytes...
October 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27818917/the-ikaros-family-of-zinc-finger-proteins
#20
REVIEW
Yingzhi Fan, Duo Lu
Ikaros represents a zinc-finger protein family important for lymphocyte development and certain other physiological processes. The number of family members is large, with alternative splicing producing various additional isoforms from each of the five homologous genes in the family. The functional forms of Ikaros proteins could be even more diverse due to protein-protein interactions readily established between family members. Emerging evidence suggests that targeting Ikaros proteins is feasible and effective in therapeutic applications, although the exact roles of Ikaros proteins remain elusive within the intricate regulatory networks in which they are involved...
November 2016: Acta Pharmaceutica Sinica. B
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