keyword
MENU ▼
Read by QxMD icon Read
search

Ikzf3

keyword
https://www.readbyqxmd.com/read/28643330/muc1-c-is-a-target-in-lenalidomide-resistant-multiple-myeloma
#1
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...
June 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28615725/transcriptome-analysis-reveals-similarities-between-human-blood-cd3-cd56-bright-cells-and-mouse-cd127-innate-lymphoid-cells
#2
David S J Allan, Ana Sofia Cerdeira, Anuisa Ranjan, Christina L Kirkham, Oscar A Aguilar, Miho Tanaka, Richard W Childs, Cynthia E Dunbar, Jack L Strominger, Hernan D Kopcow, James R Carlyle
For many years, human peripheral blood natural killer (NK) cells have been divided into functionally distinct CD3(-) CD56(bright) CD16(-) and CD3(-) CD56(dim) CD16(+) subsets. Recently, several groups of innate lymphoid cells (ILC), distinct from NK cells in development and function, have been defined in mouse. A signature of genes present in mouse ILC except NK cells, defined by Immunological Genome Project studies, is significantly over-represented in human CD56(bright) cells, by gene set enrichment analysis...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588211/transcription-factor-networks-derived-from-breast-cancer-stem-cells-control-the-immune-response-in-the-basal-subtype
#3
W A da Silveira, P V B Palma, R D Sicchieri, R A R Villacis, L R M Mandarano, T M G Oliveira, H M R Antonio, J M Andrade, V F Muglia, S R Rogatto, C Theillet, S du Manoir, D G Tiezzi
Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis from putative bCSC and reverse engineering of transcription control networks, we identified two networks associated with this phenotype. One controlled by SNAI2, TWIST1, BNC2, PRRX1 and TBX5 drives a mesenchymal or CSC-like phenotype...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588209/identification-of-the-functional-variant-driving-ormdl3-and-gsdmb-expression-in-human-chromosome-17q12-21-in-primary-biliary-cholangitis
#4
Yuki Hitomi, Kaname Kojima, Minae Kawashima, Yosuke Kawai, Nao Nishida, Yoshihiro Aiba, Michio Yasunami, Masao Nagasaki, Minoru Nakamura, Katsushi Tokunaga
Numerous genome-wide association studies (GWAS) have been performed to identify susceptibility genes to various human complex diseases. However, in many cases, neither a functional variant nor a disease susceptibility gene have been clarified. Here, we show an efficient approach for identification of a functional variant in a primary biliary cholangitis (PBC)-susceptible region, chromosome 17q12-21 (ORMDL3-GSDMB-ZPBP2-IKZF3). High-density association mapping was carried out based on SNP imputation analysis by using the whole-genome sequence data from a reference panel of 1,070 Japanese individuals (1KJPN), together with genotype data from our previous GWAS (PBC patients: n = 1,389; healthy controls: n = 1,508)...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28584254/whole-genome-sequencing-of-chronic-lymphocytic-leukemia-reveals-distinct-differences-in-the-mutational-landscape-between-ighv-mut-and-ighv-unmut-subgroups
#5
A Burns, R Alsolami, J Becq, A Timbs, D Bruce, P Robbe, D Vavoulis, M Cabes, H Dreau, J Taylor, S J L Knight, R Mansson, D Bentley, R Beekman, J I Martín-Subero, E Campo, R S Houlston, K E Ridout, A Schuh
Chronic lymphocytic leukemia (CLL) consists of two biologically and clinically distinct subtypes defined by the abundance of somatic hypermutation (SHM) affecting the Ig variable heavy chain locus (IgHV). The molecular mechanisms underlying these subtypes are incompletely understood. Here, we present a comprehensive whole genome sequencing (WGS) analysis of somatically acquired genetic events from 46 CLL patients, including a systematic comparison of coding and non-coding SNVs, CNVs and structural variants, regions of kataegis and mutation signatures between IgHV(mut) and IgHV(unmut) subtypes...
June 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28530236/psilac-mass-spectrometry-reveals-zfp91-as-imid-dependent-substrate-of-the-crl4-crbn-ubiquitin-ligase
#6
Jian An, Charles M Ponthier, Ragna Sack, Jan Seebacher, Michael B Stadler, Katherine A Donovan, Eric S Fischer
Thalidomide and its derivatives lenalidomide and pomalidomide (IMiDs) are effective treatments of haematologic malignancies. It was shown that IMiDs impart gain-of-function properties to the CUL4-RBX1-DDB1-CRBN (CRL4(CRBN)) ubiquitin ligase that enable binding, ubiquitination and degradation of key therapeutic targets such as IKZF1, IKZF3 and CSNK1A1. While these substrates have been implicated as efficacy targets in multiple myeloma (MM) and 5q deletion associated myelodysplastic syndrome (del(5q)-MDS), other targets likely exist...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28479318/identification-of-somatic-mutations-in-primary-cutaneous-diffuse-large-b-cell-lymphoma-leg-type-by-massive-parallel-sequencing
#7
Sylvain Mareschal, Anne Pham-Ledard, Pierre Julien Viailly, Sydney Dubois, Philippe Bertrand, Catherine Maingonnat, Maxime Fontanilles, Elodie Bohers, Philippe Ruminy, Isabelle Tournier, Philippe Courville, Bernard Lenormand, Anne Bénédicte Duval, Emilie Andrieu, Laurence Verneuil, Beatrice Vergier, Hervé Tilly, Pascal Joly, Thierry Frebourg, Marie Beylot-Barry, Jean-Philippe Merlio, Fabrice Jardin
To determine whether the mutational profile of primary cutaneous diffuse large B-cell lymphoma leg-type (PCLBCL-LT) is unique by comparison with other diffuse large B-cell lymphoma (DLBCL) subtypes, we analyzed a total cohort of 28 PCLBCL-LT cases by next generation sequencing with a Lymphopanel designed for DLBCL. We also analyzed 12 pairs of tumor and control DNA samples by whole exome sequencing which led us to perform resequencing of three selected genes not included in the Lymphopanel: TBL1XR1, KLHL6 and IKZF3...
May 4, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28461288/a-meta-analysis-of-genome-wide-association-studies-of-asthma-in-puerto%C3%A2-ricans
#8
Qi Yan, John Brehm, Maria Pino-Yanes, Erick Forno, Jerome Lin, Sam S Oh, Edna Acosta-Perez, Cathy C Laurie, Michelle M Cloutier, Benjamin A Raby, Adrienne M Stilp, Tamar Sofer, Donglei Hu, Scott Huntsman, Celeste S Eng, Matthew P Conomos, Deepa Rastogi, Kenneth Rice, Glorisa Canino, Wei Chen, R Graham Barr, Esteban G Burchard, Juan C Celedón
Puerto Ricans are disproportionately affected with asthma in the USA. In this study, we aim to identify genetic variants that confer susceptibility to asthma in Puerto Ricans.We conducted a meta-analysis of genome-wide association studies (GWAS) of asthma in Puerto Ricans, including participants from: the Genetics of Asthma in Latino Americans (GALA) I-II, the Hartford-Puerto Rico Study and the Hispanic Community Health Study. Moreover, we examined whether susceptibility loci identified in previous meta-analyses of GWAS are associated with asthma in Puerto Ricans...
May 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28427360/association-of-novel-polymorphisms-in-tmem39a-gene-with-systemic-lupus-erythematosus-in-a-chinese-han-population
#9
Xinze Cai, Wenyue Huang, Xudong Liu, Lining Wang, Yi Jiang
BACKGROUND: This study aimed to assess the association between 14 single nucleotide polymorphisms (SNPs) in six genes (IRF8, TMEM39A, IKZF3, ORMDL3, GSDMB, and ZPBP2) and systemic lupus erythematosus (SLE) in a Chinese Han population sample. METHODS: We carried out a case-control study of 415 patients with SLE and 470 healthy controls without autoimmune disease or cancer. DNA for genetic analysis was isolated from the blood of all subjects using standard phenol-chloroform method...
April 20, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28320958/p97-vcp-promotes-degradation-of-crbn-substrate-glutamine-synthetase-and-neosubstrates
#10
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...
April 4, 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
#11
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
#12
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
#13
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...
April 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
#14
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)...
May 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
#15
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
#16
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
#17
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
#18
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...
June 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
#19
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
#20
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
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"