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https://www.readbyqxmd.com/read/29042995/overexpression-of-dominant-negative-ikaros-6-isoform-is-associated-with-resistance-to-tkis-in-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#1
Changfeng Shao, Jie Yang, Yirong Kong, Cong Cheng, Wei Lu, Hongzai Guan, Haiyan Wang
The clinical significance of the dominant-negative Ikaros 6 (DN-IK6) in the treatment of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph(+)-ALL) with tyrosine kinase inhibitors (TKIs) remains elusive. In the present study, it was demonstrated that DN-IK6 was overexpressed in B-cell (B)-ALL cases compared with T cell-ALL cases at the mRNA and protein levels. Furthermore, nucleotide sequencing revealed that DN-IK6 was due to the deletion of IKAROS family zinc finger 1 exons 4-7. The outcome of patients with Ph(+)-B-ALL with DN-IK6, and treated with TKIs and hyper-cyclophosphamide/vincristine/doxorubicin/dexamethasone regimen were restrospectively evaluated in a 2 year follow-up...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28994305/plant-homeodomain-finger-protein-2-as-a-novel-ikaros-target-in-acute-lymphoblastic-leukemia
#2
Zheng Ge, Yan Gu, Qi Han, Justin Sloane, Qinyu Ge, Goufeng Gao, Jinlong Ma, Huihui Song, Jiaojiao Hu, Baoan Chen, Sinisa Dovat, Chunhua Song
AIM: Clinical significance of plant homeodomain finger 2 (PHF2) expressions is explored in acute lymphoblastic leukemia (ALL) patients. METHODS: mRNA level was examined by qPCR. The retroviral gene expression, shRNA knockdown and chromatin-immunoprecipitation are used to observe IKAROS regulation on PHF2 transcription. RESULTS: PHF2 expression is significantly reduced in subsets of ALL patients, and PHF2 (low) expression correlates with leukemia cell proliferation and an elevation of several poor prognostic markers in B-cell ALL...
October 10, 2017: Epigenomics
https://www.readbyqxmd.com/read/28963879/accuracy-of-serum-ige-concentrations-and-papule-diameter-in-the-diagnosis-of-cow-s-milk-allergy
#3
Jackeline M Franco, Ana Paula S G Pinheiro, Sarah C F Vieira, Íkaro Daniel C Barreto, Ricardo Q Gurgel, Renata R Cocco, Dirceu Solé
OBJECTIVE: To compare serum concentrations of specific IgE and mean papule diameters induced in the immediate skin reactivity test with cow's milk (CM) and its fractions with results of the oral challenge test (OCT), and to establish cutoff points capable of predicting clinical reactivity to CM in patients treated at a referral service. METHODS: One hundred and twenty-two children (median of 17 months) with a history of immediate reactions to CM and presence of specific IgE for CM and/or its fractions (positive skin and/or IgE serum tests) were submitted to open OCT with CM...
September 27, 2017: Jornal de Pediatria
https://www.readbyqxmd.com/read/28927821/a-novel-ikaros-haploinsufficiency-kindred-with-unexpectedly-late-and-variable-b-cell-maturation-defects
#4
Delfien J Bogaert, Hye Sun Kuehn, Carolien Bonroy, Katherine R Calvo, Joke Dehoorne, Arnaud V Vanlander, Marieke De Bruyne, Urszula Cytlak, Venetia Bigley, Frans De Baets, Elfride De Baere, Sergio D Rosenzweig, Filomeen Haerynck, Melissa Dullaers
We report on the first truncating IKZF1 mutation associated with IKAROS haploinsufficiency and illustrate an unexpectedly late and variable block in central and peripheral B cell development in two patients and their asymptomatic mother.
September 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28927157/selected-mirna-levels-are-associated-with-ikzf1-microdeletions-in-pediatric-acute-lymphoblastic-leukemia
#5
J Krzanowski, J Madzio, A Pastorczak, A Tracz, M Braun, J Tabarkiewicz, A Pluta, W Młynarski, I Zawlik
The clinical outcome of children with high-risk relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is poor. The present study assessed the utility and prognostic value of selected microRNA (miRNA/miR) in BCP-ALL. The changes in the expression levels of these miRNAs regarding known gene lesions affecting lymphoid development [early B-cell factor 1 (EBF1), ETS variant 6 (ETV6), IKAROS family zinc finger 1 (IKZF1), paired box 5 (PAX5), cyclin dependent kinase inhibitor (CDKN) 2A/CDKN2B, retinoblastoma 1 (RB1), pseudoautosomal region 1 (PAR1), B-cell translocation gene 1 protein (BTG1)] were analyzed...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927072/arsenic-trioxide-potentiates-sensitivity-of-multiple-myeloma-cells-to-lenalidomide-by-upregulating-cereblon-expression-levels
#6
Yuan Jian, Wen Gao, Chuanying Geng, Huixing Zhou, Yun Leng, Yanchen Li, Wenming Chen
The mechanism of the anti-myeloma effect of the immunomodulatory drug lenalidomide relies upon the binding of lenalidomide or an analogue to cereblon (CRBN) ubiquitin ligase, which inhibits it and results in the degradation of Ikaros-family zinc finger proteins 1 and 3 (IKZF1 and IKZF3). To determine whether the traditional Chinese medicine arsenic trioxide, could potentiate sensitivity of multiple myeloma (MM) cells to lenalidomide and identify the mechanism by which this happens, the present study investigated how arsenic trioxide affected CRBN on MM cell lines and examined the anti-myeloma effect and mechanism in the combination of arsenic trioxide and lenalidomide...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28919299/the-retrotransposon-gag-domain-containing-protein-rgag4-is-an-ikaros-target-in-the-pituitary
#7
Zhongyi Shen, Sylvia L Asa, Shereen Ezzat
Previous studies have established the common and critical involvement of the zinc finger protein Ikaros in lymphoid and pituitary cell development and expansion. Key to the assembly of several transcriptional networks, we have demonstrated up-regulation of Ikaros and its interacting partner the C-terminal Binding Protein (CtBP) in response to hypoxia. This prompted us to explore common transcriptional targets using a chromatin immunoprecipitate (ChIP) screen of DNA from pituitary corticotroph cells. This strategy yielded a finite list of targets common to both transcription factors that included the metalloprotease ADAMTS10...
September 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28914974/mucocutaneous-inflammation-in-the-ikaros-family-zinc-finger-1-ikzf1-keratin-5-specifc-transgenic-mice
#8
Mayumi Ueta, Junji Hamuro, Hiromi Nishigaki, Naomi Nakamura, Katsuhiko Shinomiya, Katsura Mizushima, Yuki Hitomi, Risa Tamagawa-Mineoka, Norihiko Yokoi, Yuji Naito, Katsushi Tokunaga, Norito Katoh, Chie Sotozono, Shigeru Kinoshita
BACKGROUND: Our genome-wide association study documented an association between cold medicine related Stevens-Johnson syndrome / toxic epidermal necrolysis (CM-SJS/TEN) and Ikaros Family Zinc Finger 1 (IKZF1). Few studies examined biological and pathological functions of IKZF1 in mucosal immunity. We hypothesized that IKZF1 contributes to the mucocutaneous inflammation. METHODS: Human skin and conjunctival tissues were obtained for immunohistological studies. Primary human conjunctival epithelial cells (PHCjECs) and adult human epidermal keratinocytes (HEKa) also used for gene expression analysis...
September 15, 2017: Allergy
https://www.readbyqxmd.com/read/28893618/lenalidomide-modulates-gene-expression-in-human-abc-dlbcl-cells-by-regulating-ikaros-interaction-with-an-intronic-control-region-of-spi-b
#9
Lauren A Solomon, Carolina R Batista, Rodney P DeKoter
Activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) is associated with a poor prognosis compared with other DLBCL types and therefore represents a top priority for developing novel therapies. Lenalidomide, an immunomodulatory drug in trials for treatment of ABC-DLBCL, targets the transcription factor IKAROS for degradation by the cereblon E3 ubiquitin ligase complex. In this study, we investigated whether the gene encoding the transcription factor SPI-B is a target of IKAROS. Using cultured ABC-DLBCL cell lines, we found that high levels of SPI-B expression conferred resistance to lenalidomide...
September 8, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28881793/lenalidomide-increases-human-dendritic-cell-maturation-in-multiple-myeloma-patients-targeting-monocyte-differentiation-and-modulating-mesenchymal-stromal-cell-inhibitory-properties
#10
Federica Costa, Rosanna Vescovini, Marina Bolzoni, Valentina Marchica, Paola Storti, Denise Toscani, Fabrizio Accardi, Laura Notarfranchi, Benedetta Dalla Palma, Cristina Manferdini, Sabrina Manni, Giannalisa Todaro, Gina Lisignoli, Francesco Piazza, Franco Aversa, Nicola Giuliani
The use of Lenalidomide (LEN), to reverse tumor-mediated immune suppression and amplify multiple myeloma-specific immunity is currently being explored. Particularly, LEN effects on dendritic cells (DCs) are still unclear. In this study, we investigated the potential effect of LEN on DC differentiation and activity. DCs were differentiated either from CD14(+) cells obtained from patients with multiple myeloma or from a human monocytic cell line. LEN, at the concentration range reached in vivo, significantly increased the median intensity expression of HLA-DR, CD86 and CD209 by DCs derived from both bone marrow and peripheral myeloma monocytes and enhanced the production of Interleukin-8, C-C motif chemokine ligand (CCL) 2, CCL5 and tumor necrosis factor-α...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28846748/plasmacytoid-dendritic-cells-and-rna-containing-immune-complexes-drive-expansion-of-peripheral-b-cell-subsets-with-an-sle-like-phenotype
#11
Olof Berggren, Niklas Hagberg, Andrei Alexsson, Gert Weber, Lars Rönnblom, Maija-Leena Eloranta
BACKGROUND: Hyperactive B cells and a continuous interferon (IFN)-α production by plasmacytoid dendritic cells (pDCs) play a key role in systemic lupus erythematosus (SLE). We asked whether the interaction between B cells and pDCs stimulated with RNA-containing immune complexes affects peripheral B cell subsets. METHODS: B cells and pDCs were isolated from blood of healthy individuals and stimulated with immune complexes consisting of SLE-IgG and U1snRNP (RNA-IC)...
2017: PloS One
https://www.readbyqxmd.com/read/28758047/the-role-of-the-ikaros-family-of-transcription-factors-in-regulatory-t-cell-development-and-function
#12
Amara Seng, Thomas M Yankee
Regulatory T (Treg) cells are a subset of immune cells that maintain homeostasis by promoting immune tolerance and suppressing the immune response via a variety of mechanisms such as secreting cytokines, killing reactive immune cells, and inducing anergy. Dysfunction of Treg cells has been implicated in inflammatory diseases such as autoimmunity and transplant rejection. Conversely, too many or hyperresponsive Treg cells has been observed in cancer and chronic infections. Treg cells have proven to be difficult to study as there are no definitive Treg surface markers...
April 2017: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/28751559/loss-of-function-but-not-dominant-negative-intragenic-ikzf1-deletions-are-associated-with-an-adverse-prognosis-in-adult-bcr-abl-negative-acute-lymphoblastic-leukemia
#13
Benjamin Kobitzsch, Nicola Gökbuget, Stefan Schwartz, Richard Reinhardt, Monika Brüggemann, Andreas Viardot, Ralph Wäsch, Michael Starck, Eckhard Thiel, Dieter Hoelzer, Thomas Burmeister
Genetic alterations of the transcription factor IKZF1 ("IKAROS") are detected in around 15-30% of cases of BCR-ABL-negative B-cell precursor acute lymphoblastic leukemia. Different types of intragenic deletions have been observed, resulting in a functionally inactivated allele ("loss-of-function") or in "dominant-negative" isoforms. The prognostic impact of these alterations especially in adult acute lymphoblastic leukemia is not well defined. We analyzed 482 well-characterized cases of adult BCR-ABL-negative B-precursor acute lymphoblastic leukemia uniformly treated in the framework of the GMALL studies and detected IKZF1 alterations in 128 cases (27%)...
October 2017: Haematologica
https://www.readbyqxmd.com/read/28751557/the-bet-bromodomain-inhibitor-cpi203-improves-lenalidomide-and-dexamethasone-activity-in-in-vitro-and-in-vivo-models-of-multiple-myeloma-by-blockade-of-ikaros-and-myc-signaling
#14
Tania Díaz, Vanina Rodríguez, Ester Lozano, Mari-Pau Mena, Marcos Calderón, Laura Rosiñol, Antonio Martínez, Natalia Tovar, Patricia Pérez-Galán, Joan Bladé, Gaël Roué, Carlos Fernández de Larrea
Most patients with multiple myeloma treated with current therapies, including immunomodulatory drugs, eventually develop relapsed/refractory disease. Clinical activity of lenalidomide relies on degradation of Ikaros and the consequent reduction in IRF4 expression, both required for myeloma cell survival and involved in the regulation of MYC transcription. Thus, we sought to determine the combinational effect of an MYC-interfering therapy with lenalidomide/dexamethasone. We analyzed the potential therapeutic effect of the combination of the BET bromodomain inhibitor CPI203 with the lenalidomide/dexamethasone regimen in myeloma cell lines...
October 2017: Haematologica
https://www.readbyqxmd.com/read/28707666/-identification-of-proteins-associated-with-transcription-factors-hoxa9-and-e2a-pbx1-by-tandem-affinity-purification
#15
E A Shestakova, M Boutin, S Bourassa, E Bonneil, J J Bijl
Chimeric transcription factor E2A-PBX1 induces the development of acute lymphoblastic B-cell leukemia in children. Using a transgenic mouse model, we previously demonstrated that homeobox (HOX) gene HOXA9 genetically interact with E2A-PBX1 gene in the development of B-cell leukemia in mice. HOXA9 itself is a potent oncogene resulting in myeloid leukemia when overexpressed, which is strongly accelerated by its collaborator Meis1. HOX, PBX1 and MEIS1 proteins have been shown to form hetero dimeric or trimeric complexes in different combinations...
May 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28696334/recent-advances-in-heart-sound-analysis
#16
Gari D Clifford, Chengyu Liu, Benjamin E Moody, José Millet Roig, Samuel E Schmidt, Qiao Li, Ikaro Silva, Roger G Mark
Heart sounds have been widely studied and have been demonstrated to have value for detecting pathologies in clinical applications. Over the last few decades, the use of heart sound signals has become increasingly uncommon and its practice in modern medicine somewhat diminished, although research into automated analysis has continued. Unfortunately, a 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...
July 11, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28670688/lack-of-ikaros-cripples-expression-of-foxo1-and-its-targets-in-naive-t-cells
#17
Parul Agnihotri, Nicholas M Robertson, Sarah E Umetsu, Ksenia Arakcheeva, Susan Winandy
Ikaros is a transcription factor that regulates lymphocyte development from the level of the haematopoietic stem cell. Lack of Ikaros reduces the ability of progenitor cells to commit to the T-cell lineage, resulting in reduced numbers of early thymic T-cell progenitors and mature T cells. Mature CD4 T cells that lack Ikaros have defects in proliferation, T helper cell differentiation, cytokine expression and the ability to become anergic. A role for Ikaros in the naive T cell has not yet been identified. The receptors interleukin-7 receptor α (IL-7Rα) and l-selectin are important for ensuring survival and proper homing of naive T cells, respectively...
November 2017: Immunology
https://www.readbyqxmd.com/read/28670491/the-transcription-factor-ikaros-inhibits-cell-proliferation-by-downregulating-anxa4-expression-in-hepatocellular-carcinoma
#18
Yi-Yao Liu, Chao Ge, Hua Tian, Jing-Yi Jiang, Fang-Yu Zhao, Hong Li, Tao-Yang Chen, Ming Yao, Jin-Jun Li
The occurrence and progression of hepatocellular carcinoma (HCC) are affected by complicated signal transduction factors. Our previous study identified Ikaros as a novel reactivated therapeutic target that acts as a transcriptional repressor and reactivates anticancer mechanisms in HCC therapy. Annexin A4 (ANXA4) is a member of the Annexin family that plays an essential role in several cancers, but it has not been investigated in HCC proliferation. Using cDNA microarrays, ANXA4 was shown to be associated with Ikaros in Ikaros-overexpressing cells...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28654293/optical-emission-in-hexagonal-sige-nanowires
#19
Xavier Cartoixà, Maurizia Palummo, Håkon Ikaros T Hauge, Erik P A M Bakkers, Riccardo Rurali
Recent advances in the synthetic growth of nanowires have given access to crystal phases that in bulk are only observed under extreme pressure conditions. Here, we use first-principles methods based on density functional theory and many-body perturbation theory to show that a suitable mixing of hexagonal Si and hexagonal Ge yields a direct bandgap with an optically permitted transition. Comparison of the calculated radiative lifetimes with typical values of nonradiative recombination mechanisms indicates that optical emission will be the dominant recombination mechanism...
July 3, 2017: Nano Letters
https://www.readbyqxmd.com/read/28643330/muc1-c-is-a-target-in-lenalidomide-resistant-multiple-myeloma
#20
Li Yin, Ashujit Tagde, Reddy Gali, Yu-Tzu Tai, Teru Hideshima, Kenneth Anderson, David Avigan, Donald Kufe
Lenalidomide (LEN) acts directly on multiple myeloma (MM) cells by inducing cereblon-mediated degradation of interferon regulatory factor 4, Ikaros (IKZF)1 and IKZF3, transcription factors that are essential for MM cell survival. The mucin 1 (MUC1) C-terminal transmembrane subunit (MUC1-C) oncoprotein is aberrantly expressed by MM cells and protects against reactive oxygen species (ROS)-mediated MM cell death. The present studies demonstrate that targeting MUC1-C with GO-203, a cell-penetrating peptide inhibitor of MUC1-C homodimerization, is more than additive with LEN in downregulating the WNT/β-catenin pathway, suppressing MYC, and inducing late apoptosis/necrosis...
September 2017: British Journal of Haematology
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