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https://www.readbyqxmd.com/read/29452225/seminars-in-cell-and-developmental-biology-human-dendritic-cell-immunodeficiencies
#1
REVIEW
Venetia Bigley, Urszula Cytlak, Matthew Collin
The critical functions of dendritic cells (DCs) in immunity and tolerance have been demonstrated in many animal models but their non-redundant roles in humans are more difficult to probe. Human primary immunodeficiency (PID), resulting from single gene mutations, may result in DC deficiency or dysfunction. This relatively recent recognition illuminates the in vivo role of human DCs and the pathophysiology of the associated clinical syndromes. In this review, the development and function of DCs as established in murine models and human in vitro systems, is discussed...
February 13, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29407587/high-frequency-of-intermediate-and-poor-risk-copy-number-abnormalities-in-pediatric-cohort-of-b-all-correlate-with-high-mrd-post-induction
#2
Minu Singh, Prateek Bhatia, Amita Trehan, Neelam Varma, Manupdesh Singh Sachdeva, Deepak Bansal, Richa Jain, Shano Naseem
Copy number abnormalities (CNAs) and recurrent fusion transcripts are important genetic events which define and prognosticate B-Cell Acute Lymphoblastic Leukemia (B-ALL). We evaluated CNAs and fusion transcripts in 67 pediatric B-ALL cases and correlated the data with standard risk factors and early treatment outcome parameters. Common fusion transcripts ETV6-RUNX1, E2A-PBX, BCR-ABL1 and MLL-AF4 were examined by RT-PCR and noted in 15%, 15%, 13% and 1.4% of all cases respectively. CNAs in IKZF1, PAX5, EBF1, BTG1, RB1, CDKN2A/B and genes from PAR1 region viz...
February 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29377892/network-based-co-expression-analysis-for-exploring-the-potential-diagnostic-biomarkers-of-metastatic-melanoma
#3
Li-Xin Wang, Yang Li, Guan-Zhi Chen
Metastatic melanoma is an aggressive skin cancer and is one of the global malignancies with high mortality and morbidity. It is essential to identify and verify diagnostic biomarkers of early metastatic melanoma. Previous studies have systematically assessed protein biomarkers and mRNA-based expression characteristics. However, molecular markers for the early diagnosis of metastatic melanoma have not been identified. To explore potential regulatory targets, we have analyzed the gene microarray expression profiles of malignant melanoma samples by co-expression analysis based on the network approach...
2018: PloS One
https://www.readbyqxmd.com/read/29363546/myeloma-cells-are-activated-in-bone-marrow-microenvironment-by-the-cd180-md-1-complex-which-senses-lipopolysaccharide
#4
Jiro Kikuchi, Yoshiaki Kuroda, Daisuke Koyama, Naoki Osada, Tohru Izumi, Hiroshi Yasui, Takakazu Kawase, Tatsuo Ichinohe, Yusuke Furukawa
Multiple myeloma (MM) cells acquire dormancy and drug resistance via interaction with bone marrow stroma cells (BMSC) in a hypoxic microenvironment. Elucidating the mechanisms underlying the regrowth of dormant clones may contribute to further improvement of the prognosis of MM patients. In this study, we find that the CD180/MD-1 complex, a non-canonical LPS receptor, is expressed on MM cells but not on normal counterparts, and its abundance is markedly upregulated under adherent and hypoxic conditions. Bacterial LPS and anti-CD180 antibody, but not other TLR ligands, enhanced the growth of MM cells via activation of MAP kinases ERK and JNK in positive correlation with expression levels of CD180...
January 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29348129/genomic-cdkn2a-2b-deletions-in-adult-ph-all-are-adverse-despite-allogeneic-stem-cell-transplantation
#5
Heike Pfeifer, Katharina Raum, Sandra Markovic, Verena Nowak, Stephanie Fey, Julia Obländer, Jovita Pressler, Verena Böhm, Monika Brüggemann, Lydia Wunderle, Andreas Hüttmann, Ralph Wäsch, Joachim Beck, Matthias Stelljes, Andreas Viardot, Fabian Lang, Dieter Hoelzer, Wolf-Karsten Hofmann, Hubert Serve, Christel Weiss, Nicola Goekbuget, Oliver G Ottmann, Daniel Nowak
We investigated the role of copy number alterations to refine risk stratification in adult Philadelphia chromosome positive (Ph)+ ALL treated with tyrosine kinase inhibitors (TKI) and allogeneic stem cell transplantation (aSCT). 97 Ph+ ALL patients (median age 41 years, range 18-64 years) within the prospective multicenter GMALL studies 06/99 (n=8) and 07/2003 (n=89) were analysed. All patients received TKI and aSCT in first complete remission (CR1). Copy number analysis was performed with SNP arrays and validated by multiplex ligation-dependent probe amplification (MLPA)...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29335448/regional-evaluation-of-childhood-acute-lymphoblastic-leukemia-genetic-susceptibility-loci-among-japanese
#6
Kevin Y Urayama, Masatoshi Takagi, Takahisa Kawaguchi, Keitaro Matsuo, Yoichi Tanaka, Yoko Ayukawa, Yuki Arakawa, Daisuke Hasegawa, Yuki Yuza, Takashi Kaneko, Yasushi Noguchi, Yuichi Taneyama, Setsuo Ota, Takeshi Inukai, Masakatsu Yanagimachi, Dai Keino, Kazutoshi Koike, Daisuke Toyama, Yozo Nakazawa, Hidemitsu Kurosawa, Kozue Nakamura, Koichi Moriwaki, Hiroaki Goto, Yujin Sekinaka, Daisuke Morita, Motohiro Kato, Junko Takita, Toshihiro Tanaka, Johji Inazawa, Katsuyoshi Koh, Yasushi Ishida, Akira Ohara, Shuki Mizutani, Fumihiko Matsuda, Atsushi Manabe
Genome-wide association studies (GWAS) performed mostly in populations of European and Hispanic ancestry have confirmed an inherited genetic basis for childhood acute lymphoblastic leukemia (ALL), but these associations are less clear in other races/ethnicities. DNA samples from ALL patients (aged 0-19 years) previously enrolled onto a Tokyo Children's Cancer Study Group trial were collected during 2013-2015, and underwent single nucleotide polymorphism (SNP) microarray genotyping resulting in 527 B-cell ALL for analysis...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29296959/somatic-mutations-in-children-with-gata2-associated-myelodysplastic-syndrome-who-lack-other-features-of-gata2-deficiency
#7
Kevin E Fisher, Amy P Hsu, Christopher L Williams, Hadi Sayeed, Brian Y Merritt, M Tarek Elghetany, Steven M Holland, Alison A Bertuch, Maria Monica Gramatges
Approximately 10% of children with primary myelodysplastic syndrome (MDS) have germ line GATA2 mutations, leading to the proposal that all children with primary MDS and certain cytogenetic findings, including monosomy 7, be tested for germ line GATA2 mutations regardless of family history or other clinical features associated with GATA2 deficiency. In adults with familial GATA2-MDS, those with somatic mutations in ASXL1 experience rapid disease progression to acute myeloid leukemia (AML) and poor prognosis after stem cell transplantation; however, the prevalence of somatic mutations in primary pediatric GATA2-MDS is unclear...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296884/changes-in-bone-marrow-innate-lymphoid-cell-subsets-in-monoclonal-gammopathy-target-for-imid-therapy
#8
Jithendra Kini Bailur, Sameet Mehta, Lin Zhang, Natalia Neparidze, Terri Parker, Noffar Bar, Tara Anderson, Mina L Xu, Kavita M Dhodapkar, Madhav V Dhodapkar
Altered number, subset composition, and function of bone marrow innate lymphoid cells are early events in monoclonal gammopathies.Pomalidomide therapy leads to reduction in Ikzf1 and Ikzf3 and enhanced human innate lymphoid cell function in vivo.
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296818/genetic-association-with-b-cell-acute-lymphoblastic-leukemia-in-allogeneic-transplant-patients-differs-by-age-and-sex
#9
Alyssa I Clay-Gilmour, Theresa Hahn, Leah M Preus, Kenan Onel, Andrew Skol, Eric Hungate, Qianqian Zhu, Christopher A Haiman, Daniel O Stram, Loreall Pooler, Xin Sheng, Li Yan, Qian Liu, Qiang Hu, Song Liu, Sebastiano Battaglia, Xiaochun Zhu, AnneMarie W Block, Sheila N J Sait, Ezgi Karaesmen, Abbas Rizvi, Daniel J Weisdorf, Christine B Ambrosone, David Tritchler, Eva Ellinghaus, David Ellinghaus, Martin Stanulla, Jacqueline Clavel, Laurent Orsi, Stephen Spellman, Marcelo C Pasquini, Philip L McCarthy, Lara E Sucheston-Campbell
The incidence and mortality rates of B-cell acute lymphoblastic leukemia (B-ALL) differ by age and sex. To determine if inherited genetic susceptibility contributes to these differences we performed 2 genome-wide association studies (GWAS) by age, sex, and subtype and subsequent meta-analyses. The GWAS included 446 B-ALL cases, and 3027 healthy unrelated blood and marrow transplant (BMT) donors as controls from the Determining the Influence of Susceptibility Conveying Variants Related to One-Year Mortality after BMT (DISCOVeRY-BMT) study...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29236701/anti-leukemic-activity-of-bortezomib-and-carfilzomib-on-b-cell-precursor-all-cell-lines
#10
Kazuya Takahashi, Takeshi Inukai, Toshihiko Imamura, Mio Yano, Chihiro Tomoyasu, David M Lucas, Atsushi Nemoto, Hiroki Sato, Meixian Huang, Masako Abe, Keiko Kagami, Tamao Shinohara, Atsushi Watanabe, Shinpei Somazu, Hiroko Oshiro, Koshi Akahane, Kumiko Goi, Jiro Kikuchi, Yusuke Furukawa, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Kanji Sugita
Prognosis of childhood acute lymphoblastic leukemia (ALL) has been dramatically improved. However, prognosis of the cases refractory to primary therapy is still poor. Recent phase 2 study on the efficacy of combination chemotherapy with bortezomib (BTZ), a proteasome inhibitor, for refractory childhood ALL demonstrated favorable clinical outcomes. However, septic death was observed in over 10% of patients, indicating the necessity of biomarkers that could predict BTZ sensitivity. We investigated in vitro BTZ sensitivity in a large panel of ALL cell lines that acted as a model system for refractory ALL, and found that Philadelphia chromosome-positive (Ph+) ALL, IKZF1 deletion, and biallelic loss of CDKN2A were associated with favorable response...
2017: PloS One
https://www.readbyqxmd.com/read/29214878/combination-of-ikzf1-deletion-and-early-molecular-response-show-significant-roles-on-prognostic-stratification-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-patients
#11
He Li, Wanhua Zhang, Pu Kuang, Yuanxin Ye, Jinjun Yang, Yang Dai, Xiaojun Lu, Yuhuan Zheng, Ting Liu
We retrospectively analyzed the samples collected from 66 patients with Ph+ALL enrolled on ChiCTR-TNRC-09000309 clinical trial. CR rate was 95.5%, and estimated 2-year OS and DFS were 51.7 ± 11.7% and 26.9 ± 11.6%, 3-year OS and DFS were 31.6 ± 12.0% and 23.4 ± 11.6%. By combining IKZF1 deletion and early molecular responses, we redefined the patients as low, intermediate, and high risk 3 groups separately. Patients with double negative in IKZF1 and early molecular response experienced significant superior survival, while patients with double positive would have the worst outcome, and patients who were one or the other with IKZF1 deletion or MRD status had intermediate outcome...
December 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29204341/case-report-exome-sequencing-identifies-t-all-with-myeloid-features-as-a-ikzf1-struck-early-precursor-t-cell-malignancy
#12
Marcus C Hansen, Line Nederby, Eigil Kjeldsen, Marianne A Petersen, Hans B Ommen, Peter Hokland
No abstract text is available yet for this article.
2018: Leukemia Research Reports
https://www.readbyqxmd.com/read/29199525/molecular-genetic-profile-in-bcr-abl1-negative-pediatric-b-cell-acute-lymphoblastic-leukemia-can-further-refine-outcome-prediction-in-addition-to-that-by-end-induction-minimal-residual-disease-detection
#13
Sanjeev Kumar Gupta, Sameer Bakhshi, Anita Chopra, Vineet Kumar Kamal
The recently proposed molecular genetic criteria promise improved risk-prediction in B-cell acute lymphoblastic leukemia (B-ALL). This study assesses their utility in BCR-ABL1 negative pediatric B-ALL, particularly with respect to end-induction minimal residual disease (MRD). The DNA was analyzed for copy number alterations in CDKN2A/B, PAX5, IKZF1, and other genes. Seventy-six cases with median age 7 years (2 months-18 years) included MRD-positive (24; 32%), and MRD negative-standard (20; 26%), intermediate (20; 26%), & high risk (12;16%) cases...
December 3, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29194562/a-risk-score-including-microdeletions-improves-relapse-prediction-for-standard-and-medium-risk-precursor-b-cell-acute-lymphoblastic-leukaemia-in-children
#14
Rosemary Sutton, Nicola C Venn, Tamara Law, Judith M Boer, Toby N Trahair, Anthea Ng, Monique L Den Boer, Anuruddhika Dissanayake, Jodie E Giles, Pauline Dalzell, Chelsea Mayoh, Draga Barbaric, Tamas Revesz, Frank Alvaro, Rob Pieters, Michelle Haber, Murray D Norris, Martin Schrappe, Luciano Dalla Pozza, Glenn M Marshall
To prevent relapse, high risk paediatric acute lymphoblastic leukaemia (ALL) is treated very intensively. However, most patients who eventually relapse have standard or medium risk ALL with low minimal residual disease (MRD) levels. We analysed recurrent microdeletions and other clinical prognostic factors in a cohort of 475 uniformly treated non-high risk precursor B-cell ALL patients with the aim of better predicting relapse and refining risk stratification. Lower relapse-free survival at 7 years (RFS) was associated with IKZF1 intragenic deletions (P < 0·0001); P2RY8-CRLF2 gene fusion (P < 0·0004); Day 33 MRD>5 × 10-5 (P < 0·0001) and High National Cancer Institute (NCI) risk (P < 0·0001)...
November 30, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29050694/the-biology-of-philadelphia-chromosome-like-all
#15
REVIEW
Kathryn G Roberts
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently described subtype of B-cell precursor ALL with a gene expression profile similar to Ph-positive ALL and a high frequency of IKZF1 alterations. The prevalence of Ph-like ALL increases with age, ranging from 10-15% of children to over 25% of young adults with ALL. It occurs more frequently in males and is associated with adverse clinical features including elevated minimal residual disease levels and poor survival in both children and adults...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/28960754/genetic-heterogeneity-of-uncharacterized-childhood-autoimmune-diseases-with-lymphoproliferation
#16
Masatoshi Takagi, Akihiro Hoshino, Kenichi Yoshida, Hiroo Ueno, Kohsuke Imai, Jinhua Piao, Hirokazu Kanegane, Motoi Yamashita, Tsubasa Okano, Hideki Muramatsu, Yusuke Okuno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Yasuhide Hayashi, Seiji Kojima, Tomohiro Morio
Autoimmune diseases in children are rare and can be difficult to diagnose.  Single causative genes have been identified for some pediatric autoimmune diseases. Such orphan diseases may not be diagnosed properly due to the variability of patients' phenotypes. Guidelines for the diagnostic process need to be developed. Fifteen patients with uncharacterized childhood autoimmune diseases with lymphoproliferation that had negative testing for autoimmune lymphoproliferative syndrome were subjected to whole-exome sequencing to identify genes associated with these conditions...
September 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28947432/ikzf1-gene-in-childhood-b-cell-precursor-acute-lymphoblastic-leukemia-interplay-between-genetic-susceptibility-and-somatic-abnormalities
#17
Bruno Almeida Lopes, Thayana Conceicao Barbosa, Bruna Kelly Santos Souza, Caroline Pires Poubel, Maria S Pombo-de-Oliveira, Mariana Emerenciano
Single nucleotide polymorphisms (SNPs) in IKZF1 are associated with inherited susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Besides, somatic copy number abnormalities (CNAs) in genes related to lymphopoiesis (e.g. IKZF1, CDKN2A/B, BTG1) impact patient's outcome. Therefore, this study aimed to investigate an association between germline susceptibility and CNAs in BCP-ALL. The IKZF1 SNPs (rs11978267 and rs4132601) were genotyped in 276 cases and 467 controls. Bone marrow samples were used to determine the presence of somatic abnormalities...
September 25, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28927821/a-novel-ikaros-haploinsufficiency-kindred-with-unexpectedly-late-and-variable-b-cell-maturation-defects
#18
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
#19
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
#20
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
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