keyword
MENU ▼
Read by QxMD icon Read
search

Ikzf3

keyword
https://www.readbyqxmd.com/read/28320958/p97-vcp-promotes-degradation-of-crbn-substrate-glutamine-synthetase-and-neosubstrates
#1
Thang Van Nguyen, Jing Li, Chin-Chun Jean Lu, Jennifer L Mamrosh, Gang Lu, Brian E Cathers, Raymond J Deshaies
Glutamine synthetase (GS) plays an essential role in metabolism by catalyzing the synthesis of glutamine from glutamate and ammonia. Our recent study showed that CRBN, a direct protein target for the teratogenic and antitumor activities of immunomodulatory drugs such as thalidomide, lenalidomide, and pomalidomide, recognizes an acetyl degron of GS, resulting in ubiquitylation and degradation of GS in response to glutamine. Here, we report that valosin-containing protein (VCP)/p97 promotes the degradation of ubiquitylated GS, resulting in its accumulation in cells with compromised p97 function...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28262390/polymorphisms-of-tgfb1-tle4-and-muc22-are-associated-with-childhood-asthma-in-chinese-population
#2
J B Chen, J Zhang, H Z Hu, M Xue, Y J Jin
OBJECTIVE: To investigate whether the genetic variants of TGFB1, TLE4, MUC22 and IKZF3 are associated with the development of asthma in Chinese children. METHODS: 572 adolescent asthma patients and 590 age-matched healthy controls were included in this study. A total of four SNPs were genotyped, including rs2241715 of TGFB1, rs2378383 of TLE4, rs2523924 of MUC22, and rs907092 of IKZF3. Allele frequencies of the patients and the control group were compared by the Chi-square test...
March 2, 2017: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/28241063/role-of-dna-methylation-in-expression-control-of-the-ikzf3-gsdma-region-in-human-epithelial-cells
#3
Sanny Moussette, Abeer Al Tuwaijri, Hamid-Reza Kohan-Ghadr, Samar Elzein, Raquel Farias, Julie Bérubé, Bianca Ho, Catherine Laprise, Cynthia G Goodyer, Simon Rousseau, Anna K Naumova
Chromosomal region 17q12-q21 is associated with asthma and harbors regulatory polymorphisms that influence expression levels of all five protein-coding genes in the region: IKAROS family zinc finger 3 (Aiolos) (IKZF3), zona pellucida binding protein 2 (ZPBP2), ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), and gasdermins A and B (GSDMA, GSDMB). Furthermore, DNA methylation in this region has been implicated as a potential modifier of the genetic risk of asthma development. To further characterize the effect of DNA methylation, we examined the impact of treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) that causes DNA demethylation, on expression and promoter methylation of the five 17q12-q21 genes in the human airway epithelium cell line NuLi-1, embryonic kidney epithelium cell line 293T and human adenocarcinoma cell line MCF-7...
2017: PloS One
https://www.readbyqxmd.com/read/28205024/immunomodulatory-drugs-in-multiple-myeloma-mechanisms-of-action-and-clinical-experience
#4
REVIEW
Sarah A Holstein, Philip L McCarthy
Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs), which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes. While thalidomide is now less commonly prescribed, lenalidomide is widely used in the treatment of newly diagnosed transplant-eligible and transplant-ineligible patients, in the maintenance setting post-transplant and in the relapsed/refractory setting, while pomalidomide is currently utilized in the relapsed/refractory setting...
February 16, 2017: Drugs
https://www.readbyqxmd.com/read/28191591/plasmacytoid-dendritic-cell-proliferations-and-neoplasms-involving-the-bone-marrow-summary-of-the-workshop-cases-submitted-to-the-18th-meeting-of-the-european-association-for-haematopathology-eahp-organized-by-the-european-bone-marrow-working-group-basel-2016
#5
Alexandar Tzankov, Konnie Hebeda, Markus Kremer, Roos Leguit, Attilio Orazi, Jon van der Walt, Umberto Gianelli
Two distinct forms of neoplasms derived from plasmacytoid dendritic cells (PDC) exist: mature PDC proliferations associated with myeloid neoplasms and blastic PDC neoplasms (BPDCN). Ten cases of PDC proliferations and neoplasms in the bone marrow have been submitted to the bone marrow workshop held at the 18th EAHP meeting. Based on observations from the submitted cases, scattered PDC (≤1% of cells) and PDC aggregates (≤10 PDC/HPF) reflect the normal bone marrow composition, while in myelodysplastic syndromes (MDS), there is a propensity for larger/more PDC aggregates (1-5% and 35 PDC/HPF)...
February 12, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28087699/activation-of-c-abl-kinase-potentiates-the-anti-myeloma-drug-lenalidomide-by-promoting-dda1-protein-recruitment-to-the-crl4-ubiquitin-ligase
#6
Shaobing Gao, Chenlu Geng, Tianyu Song, Xuanru Lin, Jiye Liu, Zhen Cai, Yong Cang
Cullin-RING ligase 4 (CRL4), a complex of Cul4 and DDB1, regulates the cell cycle, DNA damage repair, and chromatin replication by targeting a variety of substrates for ubiquitination. CRL4 is also hijacked by viral proteins or thalidomide-derived compounds to degrade host restriction factors. Here we report that the c-Abl non-receptor kinase phosphorylates DDB1 at residue Tyr-316 to recruit a small regulatory protein, DDA1, leading to increased substrate ubiquitination. Pharmacological inhibition or genetic ablation of the Abl-DDB1-DDA1 axis decreases the ubiquitination of CRL4 substrates, including IKZF1 and IKZF3, in lenalidomide-treated multiple myeloma cells...
March 3, 2017: Journal of Biological Chemistry
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
#7
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...
March 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28028022/multiple-myeloma-cells-capacity-to-decompose-h2o2-determines-lenalidomide-sensitivity
#8
Sinto Sebastian, Yuan X Zhu, Esteban Braggio, Chang-Xin Shi, Sonali C Panchabhai, Scott A Van Wier, Greg J Ahmann, Marta Chesi, P Leif Bergsagel, A Keith Stewart, Rafael Fonseca
Lenalidomide is an immunomodulatory drug (IMiDs) with clinical efficacy in multiple myeloma (MM) and other late B-cell neoplasms. Although cereblon (CRBN) is an essential requirement for IMiD action, the complete molecular and biochemical mechanisms responsible for lenalidomide-mediated sensitivity or resistance remain unknown. Here, we report that IMiDs work primarily via inhibition of peroxidase-mediated intracellular H2O2 decomposition in MM cells. MM cells with lower H2O2-decomposition capacity were more vulnerable to lenalidomide-induced H2O2 accumulation and associated cytotoxicity...
February 23, 2017: Blood
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
#9
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 60 patients with newly diagnosed multiple myeloma uniformly treated with lenalidomide in combination with intensive chemotherapy within a clinical trial...
January 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27492707/the-molecular-mechanism-of-thalidomide-analogs-in-hematologic-malignancies
#10
REVIEW
Stefanie Lindner, Jan Krönke
Thalidomide was sold in the 1950s as a sedative and was also used by pregnant women to treat morning sickness. It became notorious for causing severe birth defects and was removed from the market. More than four decades later, thalidomide had a renaissance in the treatment of cancer. Thalidomide and its more potent analogs, lenalidomide and pomalidomide, are nowadays approved treatments for multiple myeloma and myelodysplastic syndrome with deletion of chromosome 5q. In addition, thalidomide and its analogs inhibit release of tumor necrosis factor-α and increase interleukin-2 (IL-2) and interferon-γ release from T cells...
December 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27453112/-association-between-ikzf3-gene-polymorphisms-and-systemic-lupus-erythematosus-in-han-ethnic-group-in-southern-china-a-case-control-study
#11
L X Ye, C W Fu, F Jiang, W Meng
OBJECTIVE: To understand the association between IKZF3 gene polymorphism and the risk of systemic lupus erythematosus(SLE)in Han ethnic group in southern China. METHODS: A case-control study was conducted among 213 SLE patients and 234 healthy controls. Venous blood samples were collected from them to measure single nucleotide polymorphism(SNP)in IKZF3 by using the method of restriction fragment length polymorphism(PCR-RFLP). Multivariate logistic analysis and generalized multifactor dimensionality reduction(GMDR)method were used under multiple genetic models(additive, dominant, recessive), to analyze the association between IKZF3 and SLE susceptibility or different clinical features and gene-gene interactions...
July 2016: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/27302879/identification-of-master-regulator-genes-in-human-periodontitis
#12
A D Sawle, M Kebschull, R T Demmer, P N Papapanou
Analytic approaches confined to fold-change comparisons of gene expression patterns between states of health and disease are unable to distinguish between primary causal disease drivers and secondary noncausal events. Genome-wide reverse engineering approaches can facilitate the identification of candidate genes that may distinguish between causal and associative interactions and may account for the emergence or maintenance of pathologic phenotypes. In this work, we used the algorithm for the reconstruction of accurate cellular networks (ARACNE) to analyze a large gene expression profile data set (313 gingival tissue samples from a cross-sectional study of 120 periodontitis patients) obtained from clinically healthy (n = 70) or periodontitis-affected (n = 243) gingival sites...
August 2016: Journal of Dental Research
https://www.readbyqxmd.com/read/27080863/allelic-imbalance-of-multiple-sclerosis-susceptibility-genes-ikzf3-and-iqgap1-in-human-peripheral-blood
#13
Pankaj K Keshari, Hanne F Harbo, Kjell-Morten Myhr, Jan H Aarseth, Steffan D Bos, Tone Berge
BACKGROUND: Multiple sclerosis is a chronic inflammatory, demyelinating disease of the central nervous system. Recent genome-wide studies have revealed more than 110 single nucleotide polymorphisms as associated with susceptibility to multiple sclerosis, but their functional contribution to disease development is mostly unknown. RESULTS: Consistent allelic imbalance was observed for rs907091 in IKZF3 and rs11609 in IQGAP1, which are in strong linkage disequilibrium with the multiple sclerosis associated single nucleotide polymorphisms rs12946510 and rs8042861, respectively...
April 14, 2016: BMC Genetics
https://www.readbyqxmd.com/read/27070758/risk-stratification-of-t-cell-acute-lymphoblastic-leukemia-patients-based-on-gene-expression-mutations-and-copy-number-variation
#14
Gauri Mirji, Jaydeep Bhat, Jyoti Kode, Shripad Banavali, Manju Sengar, Prashant Khadke, Osama Sait, Shubhada Chiplunkar
Gene expression, copy number variations (CNV), mutations and survival were studied to delineate TCRγδ+T-cell acute lymphoblastic leukemia (T-ALL) as a distinct subgroup from TCRαβ+T-ALL. Gene Ontology analysis showed that differential regulation of genes involved in pathways for leukemogenesis, apoptosis, cytokine-cytokine receptor interaction and antigen processing/presentation may offer a survival benefit to TCRγδ+T-ALL patients. Genes involved in disease biology and having equal expression in both the subgroups, were further analysed for mutations and CNV using droplet digital PCR...
June 2016: Leukemia Research
https://www.readbyqxmd.com/read/26939566/genetic-variants-associated-with-rheumatoid-arthritis-patients-and-serotypes-in-european-populations
#15
Otsanda Ruiz-Larrañaga, Maria Uribarri, Maria C Alcaro, Sergio Escorza-Treviño, Jokin Del Amo, Mikel Iriondo, Carmen Manzano, Paola Migliorini, Veronika Lóránd, Andone Estonba
OBJECTIVES: To replicate the association of rheumatoid arthritis (RA) susceptibility loci in an independent European sample and to assess their specificity with anti-citrullinated protein antibodies (ACPA) status. METHODS: A selection of 64 SNP previously associated with RA have been typed in a cohort of 267 RA patients (169 ACPA-positive and 98 ACPA-negative) and 152 controls from the Rheumatology Units of the University Hospital of Pisa (Italy) and the University of Pécs Medical Center (Hungary)...
March 2016: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/26914976/pomalidomide-in-combination-with-dexamethasone-results-in-synergistic-anti-tumour-responses-in-pre-clinical-models-of-lenalidomide-resistant-multiple-myeloma
#16
Emily Rychak, Derek Mendy, Tao Shi, Yuhong Ning, Jim Leisten, Ling Lu, Karen Miller, Rama K Narla, Robert Z Orlowski, Heather K Raymon, Chad C Bjorklund, Anjan Thakurta, Anita K Gandhi, Brian E Cathers, Rajesh Chopra, Thomas O Daniel, Antonia Lopez-Girona
Pomalidomide is an IMiD(®) immunomodulatory agent, which has shown clinically significant benefits in relapsed and/or refractory multiple myeloma (rrMM) patients when combined with dexamethasone, regardless of refractory status to lenalidomide or bortezomib. (Schey et al, ; San Miguel et al, 2013; Richardson et al, 2014; Scott, ) In this work, we present preclinical data showing that the combination of pomalidomide with dexamethasone (PomDex) demonstrates potent anti-proliferative and pro-apoptotic activity in both lenalidomide-sensitive and lenalidomide-resistant MM cell lines...
March 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/26909574/structural-basis-of-lenalidomide-induced-ck1%C3%AE-degradation-by-the-crl4-crbn-ubiquitin-ligase
#17
Georg Petzold, Eric S Fischer, Nicolas H Thomä
Thalidomide and its derivatives, lenalidomide and pomalidomide, are immune modulatory drugs (IMiDs) used in the treatment of haematologic malignancies. IMiDs bind CRBN, the substrate receptor of the CUL4-RBX1-DDB1-CRBN (also known as CRL4(CRBN)) E3 ubiquitin ligase, and inhibit ubiquitination of endogenous CRL4(CRBN) substrates. Unexpectedly, IMiDs also repurpose the ligase to target new proteins for degradation. Lenalidomide induces degradation of the lymphoid transcription factors Ikaros and Aiolos (also known as IKZF1 and IKZF3), and casein kinase 1α (CK1α), which contributes to its clinical efficacy in the treatment of multiple myeloma and 5q-deletion associated myelodysplastic syndrome (del(5q) MDS), respectively...
April 7, 2016: Nature
https://www.readbyqxmd.com/read/26657848/immunomodulatory-drugs-act-as-inhibitors-of-dna-methyltransferases-and-induce-pu-1-up-regulation-in-myeloma-cells
#18
Shinya Endo, Masayuki Amano, Nao Nishimura, Niina Ueno, Shikiko Ueno, Hiromichi Yuki, Shiho Fujiwara, Naoko Wada, Shinya Hirata, Hiroyuki Hata, Hiroaki Mitsuya, Yutaka Okuno
Immunomodulatory drugs (IMiDs) such as thalidomide, lenalidomide, and pomalidomide are efficacious in the treatment of multiple myeloma and significantly prolong their survival. However, the mechanisms of such effects of IMiDs have not been fully elucidated. Recently, cereblon has been identified as a target binding protein of thalidomide. Lenalidomide-resistant myeloma cell lines often lose the expression of cereblon, suggesting that IMiDs act as an anti-myeloma agent through interacting with cereblon. Cereblon binds to damaged DNA-binding protein and functions as a ubiquitin ligase, inducing degradation of IKZF1 and IKZF3 that are essential transcription factors for B and T cell development...
January 8, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26544893/genetic-and-epigenetic-characterization-of-hypodiploid-acute-lymphoblastic-leukemia
#19
Setareh Safavi, Linda Olsson, Andrea Biloglav, Srinivas Veerla, Molly Blendberg, Johnbosco Tayebwa, Mikael Behrendtz, Anders Castor, Markus Hansson, Bertil Johansson, Kajsa Paulsson
PURPOSE: To investigate the genetic and epigenetic landscape of hypodiploid (<45 chromosomes) acute lymphoblastic leukemia (ALL). METHODS: Single nucleotide polymorphism array, whole exome sequencing, RNA sequencing, and methylation array analyses were performed on eleven hypodiploid ALL cases. RESULTS: In line with previous studies, mutations in IKZF3 and FLT3 were detected in near-haploid (25-30 chromosomes) cases. Low hypodiploidy (31-39 chromosomes) was associated with somatic TP53 mutations...
December 15, 2015: Oncotarget
https://www.readbyqxmd.com/read/26542096/meta-analysis-identifies-seven-susceptibility-loci-involved-in-the-atopic-march
#20
Ingo Marenholz, Jorge Esparza-Gordillo, Franz Rüschendorf, Anja Bauerfeind, David P Strachan, Ben D Spycher, Hansjörg Baurecht, Patricia Margaritte-Jeannin, Annika Sääf, Marjan Kerkhof, Markus Ege, Svetlana Baltic, Melanie C Matheson, Jin Li, Sven Michel, Wei Q Ang, Wendy McArdle, Andreas Arnold, Georg Homuth, Florence Demenais, Emmanuelle Bouzigon, Cilla Söderhäll, Göran Pershagen, Johan C de Jongste, Dirkje S Postma, Charlotte Braun-Fahrländer, Elisabeth Horak, Ludmila M Ogorodova, Valery P Puzyrev, Elena Yu Bragina, Thomas J Hudson, Charles Morin, David L Duffy, Guy B Marks, Colin F Robertson, Grant W Montgomery, Bill Musk, Philip J Thompson, Nicholas G Martin, Alan James, Patrick Sleiman, Elina Toskala, Elke Rodriguez, Regina Fölster-Holst, Andre Franke, Wolfgang Lieb, Christian Gieger, Andrea Heinzmann, Ernst Rietschel, Thomas Keil, Sven Cichon, Markus M Nöthen, Craig E Pennell, Peter D Sly, Carsten O Schmidt, Anja Matanovic, Valentin Schneider, Matthias Heinig, Norbert Hübner, Patrick G Holt, Susanne Lau, Michael Kabesch, Stefan Weidinger, Hakon Hakonarson, Manuel A R Ferreira, Catherine Laprise, Maxim B Freidin, Jon Genuneit, Gerard H Koppelman, Erik Melén, Marie-Hélène Dizier, A John Henderson, Young Ae Lee
Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12...
November 6, 2015: Nature Communications
keyword
keyword
40597
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"